On September 8, 2021 AstraZeneca PLC ("AstraZeneca") (LSE/STO/Nasdaq:AZN) reported that they have initiated SANOVO, a China Phase III study of ORPATHYS (savolitinib), an oral, potent, and highly selective MET tyrosine kinase inhibitor ("TKI"), in combination with AstraZeneca’s third-generation, irreversible epidermal growth factor receptor ("EGFR") TKI, TAGRISSO (osimertinib) as a first-line treatment in certain non-small cell lung cancer ("NSCLC") patients whose tumors harbor EGFR mutation and overexpress MET (Press release, Hutchison China MediTech, SEP 8, 2021, View Source [SID1234590537]). The first patient was dosed on September 7, 2021.

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The Phase III trial is a blinded, randomized, controlled study in previously untreated patients with locally advanced or metastatic NSCLC with activating EGFR mutations and MET overexpression. The study will evaluate the efficacy and safety of TAGRISSO in combination with ORPATHYS comparing to TAGRISSO alone, a standard-of-care treatment option for these patients. The primary endpoint of the study is median progression free survival ("PFS") as assessed by investigators. Other endpoints include median PFS assessed by an independent review committee, median overall survival ("OS"), objective response rate ("ORR"), duration of response ("DoR"), disease control rate ("DCR"), time to response (TTR), and safety. Additional details may be found at clinicaltrials.gov, using identifier NCT05009836.

About NSCLC, EGFR and MET Aberrations
Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.[1] More than a third of the world’s lung cancer patients are in China.[2] Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.[3] The majority of NSCLC patients are diagnosed with advanced disease while approximately 25-30% present with resectable disease at diagnosis.[4],[5] For patients with resectable tumors, the majority of patients eventually develop recurrence despite complete tumor resection and adjuvant chemotherapy.[6]

Approximately 10-25% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFR-mutated NSCLC.[7],[8],[9] These patients are particularly sensitive to treatment with an EGFR TKI which blocks the cell-signaling pathways that drive the growth of tumor cells.[10]

MET is a tyrosine kinase receptor.[11] Aberration of MET (amplification or overexpression) is present in both treatment naïve patients as well as being one of the primary mechanisms of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC. [12],[13]

About Savolitinib (ORPATHYS in China)
Savolitinib is an oral, potent, and highly selective MET 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 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[14]. 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[15] and final analysis was presented at the World Conference on Lung Cancer[16]. 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 ORPATHYS monotherapy in MET-driven papillary renal cell carcinoma ("RCC") (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[17]. 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[18], showing a confirmed response rate in 8 out of 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 (in planning) – Based on the encouraging results of the SAVOIR and CALYPSO studies, we are planning to initiate 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 PRCC.

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 pharmacokinetics (PK) of savolitinib in locally advanced or metastatic GC or GEJ patients whose disease progressed after at least one line of standard therapy.

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 TAGRISSO
TAGRISSO is a third-generation, irreversible EGFR TKI with clinical activity against central nervous system metastases. TAGRISSO (40mg and 80mg once-daily oral tablets) has been used to treat more than 325,000 patients across indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFR-mutated NSCLC.

In Phase III trials, TAGRISSO is being tested in the neoadjuvant resectable setting (NeoADAURA), in the Stage III locally advanced unresectable setting (LAURA) and, in combination with chemotherapy, in the Stage III locally advanced or Stage IV metastatic settings (FLAURA2). AstraZeneca is also researching ways to address tumor mechanisms of resistance through the SACHI and SANOVO Phase III trials, as well as the SAVANNAH and ORCHARD Phase II trials, which test TAGRISSO given concomitantly with savolitinib, as well as other potential new medicines.

On September 8, 2021 Candel Therapeutics, Inc. ("the Company") (Nasdaq: CADL), a late clinical stage biopharmaceutical company developing novel oncolytic viral immunotherapies, reported financial results for the second quarter ended June 30, 2021 and provided a corporate update (Press release, Candel Therapeutics, SEP 8, 2021, View Source [SID1234587591]).

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"This has been a transformational year for Candel Therapeutics as we continue to execute on our corporate strategy by advancing the development of our lead product candidate from our adenovirus platform, CAN-2409, and our lead product candidate from our HSV platform, CAN-3110, both in areas of significant unmet need," said Paul Peter Tak, M.D., Ph.D., FMedSci, President and Chief Executive Officer of Candel Therapeutics. "With the completion of our IPO in August and multiple data readouts across our broad pipeline over the next 12 months, we are in a strong position to advance our strategy and well-capitalized to support achievement of important milestones toward bringing novel immunotherapies to patients with cancer."

Second Quarter 2021 & Recent Highlights

On April 13, the Company announced formation of its new Research Advisory Board that included 2018 Nobel Laureate, James Allison, Ph.D. (MD Anderson Cancer Center), Henry Brem, M.D. (Johns Hopkins University), Roy S. Herbst, M.D., Ph.D. (Yale Cancer Center), Elizabeth Jaffee, M.D. (Johns Hopkins University), Philip Kantoff, M.D. (formerly Memorial Sloan Kettering Cancer Center), and Padmanee Sharma, M.D., Ph.D. (MD Anderson Cancer Center).
On April 22, the Company announced it completed enrollment in a phase 1 clinical trial in patients with newly diagnosed high-grade glioma to evaluate the safety and efficacy of CAN-2409 in combination with Opdivo (nivolumab) and standard of care radiation therapy, as well as temozolomide for patients who have a methylated MGMT promoter.
On June 4, the Company reported data from an ongoing phase 1 clinical trial of its oncolytic virus, CAN-3110, in patients with high-grade glioma that has recurred after initial treatment. The data presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) demonstrated a favorable safety and tolerability profile and durable responses in a number of patients.
On June 22, the U.S. Food and Drug Administration granted Fast Track designation for CAN-2409 in combination with standard-of-care surgery and chemoradiation to improve survival in adults with newly diagnosed high-grade glioma.
On July 15, the Company announced the appointment of Diem Nguyen, Ph.D., M.B.A. to its Board of Directors.
On August 17, the Company announced the completion of its Initial Public Offering, raising gross proceeds of $79.1 million, before deducting underwriting discounts and commissions and offering expenses, to support ongoing research and development efforts.
On September 7, the Company announced it completed enrollment in its phase 3 clinical trial of CAN-2409 in combination with valacyclovir for the treatment of intermediate- to high-risk localized prostate cancer.
Key Upcoming Milestones

Initial efficacy and safety data from a phase 1 clinical trial of CAN-2409 in combination with Opdivo (nivolumab) in patients with high-grade glioma are expected to be presented in the fourth quarter of 2021.
Blinded safety data from a phase 2 clinical trial of CAN-2409 in patients undergoing active surveillance for prostate cancer are expected to be presented in the third quarter of 2021.
Biomarker results from a phase 1 clinical trial of CAN-3110 in patients with recurrent high-grade glioma are expected to be presented in the fourth quarter of 2021.
Financial Results for the Second Quarter Ended June 30, 2021

Cash Position: Cash and cash equivalents as of June 30, 2021, were $24.3 million, as compared to $35.1 million as of December 31, 2020. In August 2021, Candel completed its initial public offering in which the Company issued 9,887,994 shares of common stock at a price of $8.00 per share, including the partial exercise of the underwriters’ overallotment option, for net proceeds of $71.5 million after deducting underwriting discounts and commissions and offering expenses. Based on current plans and assumptions, the Company expects its existing cash and cash equivalents, including the net proceeds of the IPO, will be sufficient to fund its operations into the second quarter of 2023.

Research & Development Expenses: Research and development expenses were $3.3 million and $6.0 million for the three and six months ended June 30, 2021, respectively, as compared to $1.8 million and $3.4 million for the comparable periods of 2020. The increases were primarily due to increased personnel-related costs for additional headcount to support the ongoing clinical trials for Candel’s product candidates as well as increased clinical development costs. Excluding stock-based compensation expense of $0.4 million for the three months ended June 30, 2021, and $0.5 million for the six months ended June 30, 2021, research and development expenses for the three and six months ended June 30, 2021, were $2.9 million and $5.5 million, respectively.

General and Administrative Expenses: General and administrative expenses were $2.0 million and $4.0 million for the three and six months ended June 30, 2021, respectively, as compared to $0.9 million and $1.6 million for the comparable periods of 2020. The increases were primarily due to increased personnel-related costs, including stock-based compensation, additional headcount required to support the growth of the Company, and an increase in professional fees associated with Candel’s preparation for the IPO completed in August 2021. Excluding stock-based compensation expense of $0.7 million for the three months ended June 30, 2021, and $ 1.0 million for the six months ended June 30, 2021, general and administrative expenses for the three and six months ended June 30, 2021, were $1.3 million and $3.0 million, respectively.

Total Operating Expenses: Total operating expenses were $5.3 million and $10.0 million for the three and six months ended June 30, 2021, respectively, as compared to $2.7 million and $5.0 million for the comparable periods of 2020. The increases were primarily due to increased personnel-related costs, including stock-based compensation, for additional headcount required to support the growth of the Company, an increase in professional fees associated with Candel’s preparation for the IPO completed in August 2021 and increased clinical development costs. Excluding stock-based compensation expense of $1.1 million for the three months ended June 30, 2021, and $1.5 million for the six months ended June 30, 2021, total operating expenses for the three and six months ended June 30, 2021, were $4.2 million and $8.5 million, respectively.

Net Loss: Net loss was $17.1 million and $21.6 million for the three and six months ended June 30, 2021, respectively, as compared to $2.9 million and $4.6 million for the comparable periods of 2020. The net loss for the three and six months ended June 30, 2021, includes a noncash charge of $12.4 million for the change in the fair value of the Company’s warrant liability and stock-based compensation of $1.1 million and $1.5 million, respectively. Excluding the noncash charges for the change in the warrant liability and stock-based compensation, the net loss for the three and six months ended June 30, 2021, was $3.6 million and $7.7 million, respectively.

On September 8, 2021 BeyondSpring Inc. ("BeyondSpring") (NASDAQ: BYSI), a global biopharmaceutical company focused on the development of innovative cancer therapies, reported that management will present at and participate in the Morgan Stanley 19th Annual Global Healthcare Conference and R.W. Baird’s 2021 Global Healthcare Conference (Press release, BeyondSpring Pharmaceuticals, SEP 8, 2021, View Source;utm_medium=rss&utm_campaign=beyondspring-to-participate-in-the-upcoming-september-conferences [SID1234587570]). Details for both conferences are below:

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Morgan Stanley 19th Annual Global Healthcare Conference
Date: Tuesday, September 14th 2021
Time: 11:45am ET
Format: Fireside Chat
Management will also be available for 1×1 meetings on September 9th-15th, 2021. If you would like to request a meeting, please contact [email protected].

R.W. Baird’s 2021 Global Healthcare Conference
Date: Wednesday, September 15th 2021
Time: 4:55pm ET
Format: Presentation
Management will also be available for 1×1 meetings on September 14th-15th, 2021. If you would like to request a meeting, please contact [email protected].

On September 8, 2021 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutic candidates that have the potential to transform radiotherapy in cancer, reported final results from its Phase 1/2 pilot trial of its dismutase mimetic, GC4419, versus placebo, in patients with unresectable or borderline resectable locally advanced pancreatic cancer (LAPC), who are undergoing stereotactic body radiation therapy (SBRT) (Press release, Galera Therapeutics, SEP 8, 2021, View Source [SID1234587531]). The results include a minimum of one year of follow up on all 42 patients enrolled in the trial.

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In this proof-of-concept trial, improvements were observed in overall survival (HR=0.48; 95% CI: 0.20-1.14; p=0.090), progression-free survival (HR=0.46; 95% CI: 0.22-0.98; p=0.040), local tumor control (HR=0.30; 95% CI: 0.08-1.10; p=0.055) and time to distant metastases (HR=0.39; 95% CI: 0.16-0.93; p=0.028). 46% of patients in the active arm were alive at last follow-up (11 out of 24) compared to 33% in the placebo arm (6 out of 18). As previously reported, 29% of patients in the active arm achieved a 30% or greater decrease in primary tumor size (partial response) compared to 11% of patients in the placebo arm. GC4419 was well tolerated, with similar rates of early and late adverse events in the active and placebo arms. For more information related to this trial, please see the Company’s updated corporate presentation on the Investors page of Galera’s website at investors.galeratx.com.

"We are very pleased with the survival and tumor outcome benefits observed in the final analysis of this proof-of-concept trial," said Mel Sorensen, M.D., President and CEO of Galera. "The improvements across multiple efficacy parameters, together with the safety data, are encouraging and underpin the rationale for our 160-patient blinded, randomized GRECO-2 trial of GC4711 with SBRT in pancreatic cancer, where the primary endpoint is overall survival. These are exciting times for Galera as we also look forward to announcing topline data from our ROMAN Phase 3 trial for the reduction of severe oral mucositis in patients with head and neck cancer later this year."

"We are excited to see the final results from this trial and enthusiastic to participate in the Phase 2b GRECO-2 trial," said Sarah Hoffe, M.D., Section Head of GI Radiation Oncology at H. Lee Moffitt Cancer Center and Research Institute. "These observed overall survival rates are particularly encouraging in pancreatic cancer, as this patient population faces a difficult diagnosis with high rates of distant metastasis and low rates of cure."

Galera’s selective dismutase mimetic product candidates are small molecules being developed to protect normal cells and sensitize cancer cells to radiotherapy. The Phase 1/2 pilot trial was a randomized, double-blind, multicenter, placebo-controlled trial in 42 patients diagnosed with LAPC evaluating the safety and efficacy of SBRT and the dismutase mimetic, GC4419, compared to SBRT and placebo. Patients were randomized (1:1) to receive GC4419 or placebo by intravenous infusion one hour prior to SBRT.

GRECO-2 is a randomized, double-blind, placebo-controlled Phase 2b trial evaluating Galera’s second dismutase mimetic product candidate, GC4711, compared to placebo in patients with LAPC undergoing SBRT. The trial was initiated in May 2021 and is expected to enroll approximately 160 patients. The primary endpoint of the trial is overall survival. Secondary endpoints include progression-free survival, local tumor control, time to distant metastases and surgical resection rate, in addition to safety.

On September 8, 2021 Galera Therapeutics presented Corporate Presentation (Presentation, Galera Therapeutics, SEP 8, 2021, View Source [SID1234587504]).

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