On September 17, 2021 AstraZeneca reported that Results from the large, randomised COAST Phase II trial showed oleclumab, an anti-CD73 monoclonal antibody, or monalizumab, an anti-NKG2A monoclonal antibody, in combination with Imfinzi (durvalumab) improved progression-free survival (PFS) and objective response rate (ORR) compared to Imfinzi alone in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) who had not progressed after concurrent chemoradiation therapy (CRT) (Press release, AstraZeneca, SEP 17, 2021, View Source [SID1234587872]).

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After a median follow-up of 11.5 months, the results of an interim analysis showed Imfinzi in combination with oleclumab reduced the risk of disease progression or death by 56% (hazard ratio [HR] of 0.44; 95% confidence interval [CI] 0.26-0.75), and in combination with monalizumab by 35% (HR of 0.65; 95% CI 0.49-0.85), when compared to Imfinzi alone in Stage III NSCLC patients following CRT. The 10-month PFS rate was 64.8% for the durvalumab plus oleclumab combination and 72.7% for durvalumab plus monalizumab, versus 39.2% with durvalumab alone.

The results, presented during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 today, also showed an increase in the primary endpoint of confirmed ORR for Imfinzi plus oleclumab over Imfinzi alone (30% vs. 18%) and for Imfinzi plus monalizumab over Imfinzi alone (36% vs. 18%).

One in four patients with NSCLC are diagnosed at Stage III, where the majority of tumours are unresectable (cannot be removed with surgery).1,2 Imfinzi after CRT is the global standard of care for patients in this setting, based on the PACIFIC Phase III trial.3-5

Roy S. Herbst, MD, PhD, Chief of Medical Oncology at Yale Cancer Center and Smilow Cancer Hospital, New Haven, CT and Chair of the COAST Steering Committee said: "Imfinzi is the established standard of care for patients with unresectable, Stage III NSCLC, but solutions are still needed for patients who do not benefit from currently available therapies. The remarkable improvement observed with the addition of oleclumab or monalizumab to Imfinzi, along with the strong safety profile, suggests these novel combinations could further redefine outcomes for these patients."

Susan Galbraith, Executive Vice President, Oncology R&D, said: "Imfinzi has transformed the treatment of patients with unresectable, Stage III NSCLC, and we’re excited by the promise of extending its benefit through novel combinations with two potential first-in-class monoclonal antibodies demonstrating strong clinical activity. Based on the stand-out results from COAST, we plan to start a registrational trial with the hope of bringing these new treatment options to patients that further increase the potential for cure in this setting."

Safety was similar across treatment arms with no new safety signals identified for either Imfinzi combination. Incidence of Grade 3 or higher treatment-emergent adverse events (TEAE; all cause) were 39.4% with Imfinzi, 40.7% with Imfinzi plus oleclumab, and 27.9% with Imfinzi plus monalizumab.

The most common Grade 3/4 TEAE was dyspnoea (reported in 3.0%, 1.7% and 1.6% of patients, respectively). Grade 3/4 pneumonitis was only reported for one patient (1.6%), who received Imfinzi plus monalizumab.

PACIFIC-real world observational study (PACIFIC-R) demonstrated benefit of Imfinzi in real-world setting at the ESMO (Free ESMO Whitepaper) Congress 2021
Data from a planned analysis of real-world PFS (rwPFS) from the PACIFIC-R observational study was also presented during ESMO (Free ESMO Whitepaper), showing the first effectiveness data from over a thousand patients with unresectable, Stage III NSCLC who were treated with Imfinzi in the real-world setting as part of AstraZeneca’s global PACIFIC Early Access Programme. The analysis showed a median rwPFS of 21.7 months in the real-world setting.

In comparison, a median PFS of 16.9 months was observed among patients treated with Imfinzi in the randomised, double-blinded, placebo-controlled PACIFIC Phase III trial. These results demonstrate the long-term effectiveness of Imfinzi in this real-world patient population and reinforce the PACIFIC regimen as the established standard of care today following platinum-based CRT.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after CRT in the US, Japan, China, across the EU and in many other countries with more than 80,000 patients treated with Imfinzi in this setting since its first approval in February 2018. Imfinzi is also approved for the 1st-line treatment of extensive-stage small cell lung cancer (ES-SCLC) in combination with etoposide and either carboplatin or cisplatin in more than 55 countries, including the US, Japan, China and across the EU, based on the CASPIAN Phase III trial.

AstraZeneca has several ongoing registrational trials focused on evaluating Imfinzi in earlier stages of lung cancer, including in potentially curative settings (PACIFIC-2, 4 and 5, MERMAID-1 and 2, AEGEAN, ADJUVANT BR.31, and ADRIATIC Phase III trials). The Company is also testing novel combinations with Imfinzi in the Phase II NeoCOAST trial in the neoadjuvant early-stage setting.

Stage III NSCLC
In 2020, an estimated 2.2 million people were diagnosed with lung cancer worldwide.6 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.2,3,7 Stage III NSCLC represents approximately one quarter of NSCLC incidence.1

Stage III (locally advanced) NSCLC is commonly divided into three subcategories (IIIA, IIIB and IIIC), defined by how much the cancer has spread locally. In contrast to Stage IV, when cancer has spread (metastasised), the majority of Stage III patients are currently treated with curative intent.2,8

The majority of Stage III NSCLC patients are diagnosed with unresectable tumours.1,2 Prior to the approval of Imfinzi in this setting, no new treatments beyond CRT had been available to these patients for decades.3-5

COAST
COAST is a Phase II, multi-arm, randomised trial investigating Imfinzi alone or in combination with either oleclumab (anti-CD73 monoclonal antibody) or monalizumab (anti-NKG2A monoclonal antibody) in 189 patients with locally advanced, unresectable Stage III NSCLC who had not progressed after CRT.

COAST is being conducted in 82 centres across 9 countries in North America, Europe and Asia. The primary endpoint of the trial is ORR as a measure of anti-tumour activity. Secondary endpoints include safety, duration of response, overall survival and PFS.

PACIFIC-R
PACIFIC-Real World (PACIFIC-R) is an international, observational study of 1,399 patients with unresectable, Stage III NSCLC previously treated with Imfinzi as part of an early access program (EAP) between September 2017 and December 2018. Patients were enrolled in the PACIFIC-R study after discontinuation of the EAP in participating countries. Eligible patients had not progressed after CRT and were enrolled regardless of PD-L1 status at trial initiation.

Imfinzi
Imfinzi is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to approvals in unresectable, Stage III NSCLC and ES-SCLC, Imfinzi is also approved for previously treated patients with advanced bladder cancer in several countries.

As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with NSCLC, SCLC, bladder cancer, hepatocellular carcinoma, biliary tract cancer (a form of liver cancer), oesophageal cancer, gastric and gastroesophageal cancer, cervical cancer, ovarian cancer, endometrial cancer, and other solid tumours.

Oleclumab
Oleclumab is a potentially first-in-class, anti-CD73 monoclonal antibody that selectively binds to and inhibits the activity of CD73. CD73 is a cell surface enzyme which is overexpressed in the tumour microenvironment and promotes tumour growth by limiting anti-tumour immunity via the adenosine receptor pathway.

Preclinical studies have demonstrated that CD73 blockade improved anti-tumour activity in combination with radiotherapy, chemotherapy and immunotherapy. Oleclumab is also being examined in various Phase II trials for solid tumour malignancies.

Monalizumab
Monalizumab is a potentially first-in-class, anti-NKG2A antibody. NKG2A is a checkpoint receptor expressed on tumour-infiltrating cytotoxic T-cells and natural killer cells that inhibits their anti-cancer functions.

Monalizumab is also being studied in the ongoing INTERLINK-1 Phase III trial, evaluating monalizumab in combination with cetuximab for the treatment of patients with previously-treated recurrent or metastatic head and neck squamous cell carcinoma.

Monalizumab is being developed in collaboration with Innate Pharma. AstraZeneca obtained full oncology rights to monalizumab in October 2018 through a co-development and commercialisation agreement initiated in 2015.

AstraZeneca in lung cancer
AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi and tremelimumab; Enhertu (trastuzumab deruxtecan) and datopotamab deruxtecan in collaboration with Daiichi Sankyo; Orpathys (savolitinib) in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

AstraZeneca in immunotherapy
Immunotherapy is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. The Company’s Immuno-Oncology (IO) portfolio is anchored in immunotherapies that have been designed to overcome anti-tumour immune suppression. AstraZeneca is invested in using IO approaches that deliver long-term survival for new groups of patients across tumour types.

The Company is pursuing a comprehensive clinical-trial programme that includes Imfinzi as a single treatment and in combination with tremelimumab and other novel antibodies in multiple tumour types, stages of disease, and lines of treatment, and where relevant using the PD-L1 biomarker as a decision-making tool to define the best potential treatment path for a patient. In addition, the ability to combine the IO portfolio with radiation, chemotherapy, small, targeted molecules from across AstraZeneca’s oncology pipeline, and from research partners, may provide new treatment options across a broad range of tumours.

AstraZeneca in oncology
AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

On September 17, 2021 MaxCyte, Inc., (NASDAQ: MXCT; LSE: MXCT, MXCN), a leading commercial cell engineering company focused on providing enabling platform technologies to advance innovative cell-based research as well as next-generation cell therapeutic discovery, development and commercialization, reported its financial results for its second quarter and six months ended June 30, 2021 (Press release, MaxCyte, SEP 17, 2021, View Source [SID1234587889]).

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Second Quarter & Recent Highlights

Total revenue of $7.1 million in the second quarter of 2021, representing 38% growth compared to the same period in 2020
Excluding SPL Program-related revenue, revenue from cell therapy customers was $4.8 million for the second quarter, an increase of 59% year-over-year, while revenue from drug discovery customers was $1.8 million in the second quarter, an increase of 60% year-over-year. SPL Program-related revenue was $0.5 million in the second quarter, as compared to $1.0 million for the same period in 2020
Signed two new SPL agreements with Celularity, Inc. (Q2) and Sana Biotechnology, Inc. (Q3) for the use of MaxCyte’s Flow Electroporation ExPERT platform to advance cellular research and development of cell-based therapies
Expanded Board of Directors with the appointment of Ms. Rekha Hemrajani and Dr. Yasir Al-Wakeel
Completed U.S. initial public offering on Nasdaq Global Select Stock Market, raising $201.8 million in gross proceeds
"We are pleased to report strong second quarter and half year results driven by growth in instrument revenue and disposable sales to the cell therapy market as our cell therapy partners continue to progress into and through the clinic. We also saw a resurgence of growth in drug discovery customers as new disposables introduced in 2020 have started to gain traction, driving both instrument and disposable sales growth," said Doug Doerfler, President and CEO of MaxCyte.

"Our customer base is expanding and we continue to increase the number of strategic partnerships. We now have 14 SPL agreements covering over 75 potential clinical programs, which is a testament to MaxCyte’s reputation as a leading collaborator for complex cellular engineering. With the proceeds from our IPO in the U.S., MaxCyte is well-positioned to support growing adoption of the ExpertTM platform technology for cellular-based research and next-generation therapeutic development."

Second Quarter Financial Results

Total revenue for the second quarter of 2021 was $7.1 million, compared to $5.2 million in the second quarter of 2020, representing year-over-year growth of 38%. Overall sales to the cell therapy (up 59%) and the drug discovery (up 60%) markets were each sources of strength in the quarter.

The Company recognized $0.5 million in Program-related revenue in the quarter (comprised of pre-commercial milestone revenues) as compared to $1.0 million in Program-related revenue in the second quarter of 2020.

Gross profit for the second quarter of 2021 was $6.3 million (89% gross margin), compared to $4.7 million (91% gross margin) in the same period of the prior year. The slight decline in gross margin was driven by the reduction in SPL Program-related revenues; excluding SPL Program-related revenues, gross margin was relatively unchanged.

Operating expenses for the second quarter of 2021 were $10.7 million, compared to operating expenses of $7.5 million in the second quarter of 2020. The overall increase in operating expense was principally driven by a $3.3 million increase in compensation expense associated with increased headcount and higher stock-based compensation (principally due to stock-price appreciation), as well as a $1.0 million increase in legal and professional service expenses. Partially offsetting this expense growth was a $1.9 million decline in CARMA-related expenses compared with the same period last year. As of March 2021, all pre-clinical and clinical activities related to the CARMA platform were substantially completed.

Second quarter 2021 net loss was ($4.4) million compared to net loss of ($3.0) million for the same period in 2020.

Total cash, cash equivalents and short-term investments was $73.4 million as of June 30, 2021 excluding the $201.8 million in gross proceeds from the U.S. IPO that closed in August 2021.

Preliminary 2021 Revenue

Following our recent IPO on the Nasdaq, the company is establishing an initial projection of total revenue of approximately $30 million for fiscal year 2021.

First Half 2021 Financial Results

Total revenue for the first half of 2021 was $13.6 million, compared to $10.9 million in the first half of 2020, representing year-over-year growth of 25%. Overall sales to the cell therapy (up 53%) and the drug discovery (up 22%) markets were each sources of strength in the first half.

The Company recognized $0.5 million in Program-related revenue in the first half (comprised of pre-commercial milestone revenues) as compared to $1.8 million in Program-related revenue in the first half of 2020.

Gross profit for the first half of 2021 was $12.1 million (89% gross margin), compared to $9.8 million (90% gross margin) in the same period of the prior year. The slight decline in gross margin was driven by the reduction in SPL Program-related revenues; excluding SPL Program-related revenues, gross margin was relatively unchanged.

Operating expenses for the first half of 2021 were $22.9 million, compared to operating expenses of $15.6 million in the first half of 2020. The overall increase in operating expense was principally driven by a $5.8 million increase in compensation expense associated with increased headcount and higher stock-based compensation (principally due to stock-price appreciation), as well as a $1.4 million increase in legal and professional service expenses. Partially offsetting this expense growth was a $0.8 million decline in CARMA-related expenses compared with the same period last year. As of March 2021, all pre-clinical and clinical activities related to the CARMA platform were substantially completed.

First half 2021 net loss was ($11.5) million compared to net loss of ($6.1) million for the same period in 2020.

Webcast and Conference Call Details

MaxCyte will host a conference call today, September 13, 2021, at 4:30 p.m. Eastern Time. Interested parties may access the live teleconference by dialing (844) 679-0933 for domestic callers or (918) 922-6914 for international callers, followed by Conference ID: 3199124. A live and archived webcast of the event will be available on the "Events" section of the MaxCyte website at View Source

On September 17, 2021 Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases, reported that the interim analysis results of the Phase 3 ORIENT-15 study evaluating sintilimab in combination with chemotherapy for the first-line treatment of esophageal squamous cell carcinoma (ESCC) were released today in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2021 (Abstract # LBA52) (Press release, Innovent Biologics, SEP 17, 2021, View Source [SID1234587907]).

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All endpoints of ORIENT-15 were met at the interim analysis. As of the April 9, 2021 data cutoff, 659 patients were randomly assigned and received treatment. Sintilimab plus chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]) resulted in a superior median overall survival (mOS) over placebo plus chemotherapy in all randomized patients (the ITT population) (16.7 vs 12.5 months, respectively; HR 0.628; P<0.0001) and in PD-L1 positive patients (defined as combined positive score [CPS] ≥10) (17.2 vs 13.6 months, respectively; HR 0.638; P=0.0018). Sintilimab plus chemotherapy significantly improved median progression-free survival (mPFS) in all randomized patients (7.2 vs 5.7 months, respectively; HR 0.558; P<0.0001) and in PD-L1 positive patients (8.3 vs 6.4 months, respectively; HR 0.580; P<0.0001). The safety profile of sintilimab in this study was consistent with that observed in previously reported studies of sintilimab, and no additional safety signals were identified for the combination of sintilimab and chemotherapy.

The principal investigator of the ORIENT-15 study, Prof. Shen Lin from Peking University Cancer Hospital and Institute, stated, "More than half of new and fatal cases of esophageal cancer in the world occur in China every year. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, and squamous cell carcinoma is the predominant histologic type. The treatment options for locally advanced or metastatic ESCC are limited and represent a significant unmet clinical need. The ORIENT-15 results suggest that sintilimab in combination with chemotherapy may represent a first-line treatment option for patients with advanced or metastatic ESCC."

Dr. Hui Zhou, Senior Vice President of Innovent, stated, "We thank the investigators and study team for their joint effort and, most importantly, we would like to express our sincere gratitude to all the patients who participated in the ORIENT-15 study. We have submitted an application to the National Medical Products Administration (NMPA) of China in early September based on these results, and hope that sintilimab plus chemotherapy can become a first-line treatment option for ESCC patients in the near future ."

About the ORIENT-15 Study

ORIENT-15 is a global randomized, double-blind, multicenter Phase 3 clinical study evaluating sintilimab in combination with chemotherapy (cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil [5-FU]), compared to placebo in combination with chemotherapy, for the first-line treatment of unresectable locally advanced, recurrent or metastatic esophageal squamous cell carcinoma (ClinicalTrials.gov, NCT03748134). At the time of interim analysis, a total of 659 eligible patients (of the planned 676 estimated participants) were enrolled and randomly assigned into the experimental group or control group in a 1:1 ratio. The primary endpoints were overall survival (OS) in all randomized patients and OS in PD-L1 positive (defined as CPS ≥10) patients.

About Esophageal Squamous Cell Carcinoma (ESCC)

Esophageal cancer (EC) is one of the most common malignant tumors worldwide that begins in the inner layer (mucosa) of the esophagus, which connects the throat to the stomach. Based on GLOBOCAN 2020 estimates, approximately 600,000 new cases of esophageal cancer are diagnosed and approximately 540,000 deaths result from the disease worldwide each year. Esophageal cancer is the seventh most commonly diagnosed cancer and the sixth leading cause of death from cancer worldwide. More than half of new and fatal cases of esophageal cancer in the world occur in China. In China, it is estimated there were approximately 320,000 new cases of esophageal cancer diagnosed and approximately 300,000 deaths resulting from the disease in 2020. Esophageal cancer is the fifth most commonly diagnosed cancer and the fourth leading cause of death from cancer in China, where it has a five-year survival rate of only 30%. In the US, it is estimated there were approximately 18,000 new cases of esophageal cancer diagnosed and approximately 16,000 deaths resulting from the disease in 2020. The five-year survival rate of esophageal cancer is only 20% in the US.

The two main types of esophageal cancer are squamous cell carcinoma (SCC) and adenocarcinoma. In China, SCC is the predominant histologic type, accounting for more than 90% of all esophageal cancer. In western countries, SCC is approximately 25% of all esophageal cancer. In the past first-line standard systemic therapy was chemotherapy based on platinum drugs for unresectable locally advanced, recurrent or metastatic ESCC. Pembrolizumab has been approved as first-line treatment in combination with chemotherapy.

About Sintilimab

Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has three clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
In combination with oxaliplatin and capecitabine for the first-line treatment of unresectable, locally advanced, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

On September 17, 2021 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company developing next generation cancer and infectious disease immunotherapies, reported updated results from the Phase 1/2 study evaluating the safety, immunogenicity, and clinical activity of GRANITE individualized neoantigen immunotherapy (heterologous prime-boost in combination with PD-1 checkpoint inhibitor Opdivo [nivolumab] and subcutaneous anti-CTLA-4 antibody Yervoy [ipilimumab]) in advanced solid tumors (Press release, Gritstone Oncology, SEP 17, 2021, View Source [SID1234592014]). The data were presented during a mini-oral presentation by investigator and Associate Professor of Medicine at the University of Chicago, Dan Catenacci, MD, as part of the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Annual Meeting.

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In the 26 patients treated in the study with metastatic solid tumors largely focused on MSS-CRC and gastro-esophageal adenocarcinoma (GEA), GRANITE immunotherapy demonstrated good tolerability, consistent and potent immunogenicity (CD8+ neoantigen-specific T cell induction in all subjects), and objective evidence of efficacy as measured by reduction in ctDNA (molecular response). In particular, MSS-CRC patients exhibited "cold" tumors at baseline, with low PD-L1 and IFN-g expression and low tumor mutational burden.

Based on these data, Gritstone has discussed the registrational path with the U.S. Food & Drug Administration (FDA), and is advancing GRANITE into a randomized, controlled, phase 2/3 clinical trial (single protocol) for the maintenance treatment of newly diagnosed metastatic MSS-CRC patients who have completed FOLFOX-bevacizumab induction therapy. Additionally, the company will conduct a separate randomized, controlled phase 2 trial evaluating GRANITE in the adjuvant setting for stage II/III MSS-CRC patients who are ctDNA+ after definitive surgery. The trials are expected to begin in the first half of 2022. The checkpoint inhibitors being used for these studies have not yet been disclosed.

"GRANITE is demonstrating a favorable safety and tolerability profile and is consistently inducing high numbers of neoantigen-specific CD8+ T cells" said Andrew Allen, MD, PhD, Gritstone’s Co-Founder and CEO. "Most strikingly, even in these advanced patients, there is clear evidence of tumor destruction as measured by reduction in ctDNA, a sensitive biomarker of disease burden. Furthermore, in a disease setting such as MSS-CRC that does not respond to checkpoint blockade therapy, our patients with GRANITE-induced molecular responses appear to be living longer, providing hope where historically there has been very little."

As of the August 5, 2021 data cutoff, the GRANITE Phase 1/2 study treated 26 patients; 14 in the Phase 1 dose escalation portion, and 12 in the Phase 2 portion across three tumor-specific expansion cohorts – MSS-CRC, gastroesophageal adenocarcinoma (GEA), and non-small cell lung cancer (NSCLC). All patients receive Gritstone’s proprietary heterologous prime-boost consisting of Chimpanzee Adenovirus Vector (ChAdV) and Self-Amplifying mRNA (SAM) in combination with intravenous nivolumab and subcutaneous ipilimumab.

In MSS-CRC patients, where checkpoint inhibitors have shown minimal activity, GRANITE elicited a 44% molecular response rate in 9 evaluable patients (defined as a 50% or greater reduction in ctDNA from baseline) which is an increasingly well recognized objective efficacy biomarker for novel immunotherapy. Patients who demonstrated molecular response had median overall survival of >17 months (median not reached) whereas those without molecular response exhibited a median overall survival of 7.8 months, consistent with expected outcomes in 3rd line treatment of MSS-CRC.

MSS-CRC All (n=121) No Molecular Response (n=5) Molecular Response (n=4)
Median Overall Survival (months) 8.7 7.8 Not reached (>17)
Median iPFS per iRECIST (months) 3.9 2.0 11.8
Median PFS per RECIST (months) 2.0 2.0 4.9
i=immune-based; PFS = progression-free survival; RECIST=Response Evaluation Criteria in Solid Tumors
1. 12 MSS-CRC patients treated; 9 patients eligible for analysis of ctDNA changes relative to baseline

A confirmed complete RECIST response was observed in a GEA patient (ctDNA negative at baseline). Multiple patients remained on treatment for over 6 months with lack of confirmed disease progression including 2/9 MSS-CRC patients receiving treatment beyond 12 months and one patient currently at 11+ months, which contrasts sharply with the expected outcome for these patients. 50% of patients (3/6) had a slow decrease in volume of multiple pulmonary metastasis during the first year of therapy, even though these objective radiological responses did not meet RECIST criteria. These radiological observations were associated with prolonged time on study and decrease in biomarkers such as ctDNA.

"The unmet need in our many patients with metastatic colorectal cancer is profound –third-line therapy offers limited additional benefit and checkpoint inhibitors are ineffective in this setting" said Dr. Daniel Catenacci. "The early, but strikingly consistent, clinical and translational data from the Gritstone program are very encouraging, and the suggestion that immunologically cold tumors can become viable targets for the immune system could be a game-changer in treating MSS-CRC. I am excited to see how well GRANITE can perform in healthier, earlier-stage patients where we expect to see fewer patients progress rapidly before active immunotherapy."

Additional information about the trial can be found at www.clinicaltrials.gov, NCT03639714

Opdivo and Yervoy are trademarks of Bristol-Myers Squibb Company.

Webcast Information
To register for the webinar, please click here. The call and accompanying slides will be webcast live on the "Events" page under the "Investors & Media" section of the company’s website at www.gritstone.com. A replay of the webcast will be accessible at the same link approximately one day after its completion.

About GRANITE
Gritstone’s neoantigen-based immunotherapies are engineered to elicit a significant T-cell response (particularly CD8+ cytotoxic T cells) against mutation-derived tumor-specific neoantigens, or TSNA, that are identified by the company using its proprietary Gritstone EDGETM artificial intelligence platform and tumor HLA peptide sequencing. GRANITE is an individualized neoantigen-based immunotherapy and uses a priming adenoviral vector (GRT-C901) and self-amplifying mRNA vector (GRT-R902) to deliver personalized immunotherapy containing the relevant neoantigens. It is being evaluated in the Phase 2 portion of a Phase 1/2 clinical study in combination with checkpoint inhibitors for patients with microsatellite stable colorectal cancer (MSS CRC) who have progressed on FOLFOX/FOLFIRI therapy and a second cohort for patients with gastro-esophageal cancer who have progressed on chemotherapy (NCT03639714). GRANITE was granted Fast Track designation by the U.S. Food and Drug Administration for the treatment of MSS CRC.

On September 17, 2021 Midatech Pharma PLC (AIM: MTPH.L; NASDAQ: MTP), a drug delivery technology company focused on improving the bio-delivery and biodistribution of medicines, reported its unaudited interim results for the six months ended 30 June 2021 (Press release, Midatech Pharma, SEP 17, 2021, View Source [SID1234587890]).

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OPERATIONAL HIGHLIGHTS

On 17 June 2021, the Company announced significant progress across a number of R&D programmes including:

Q-Sphera

·Breakthrough data on the successful encapsulation of an exemplar monoclonal antibody (mAb);

·The delivery of proof of concept formulations of MTX214 and MTX216 to the Company’s collaboration partner for the partner’s in vivo studies; and

·The successful development of MTD211, a long-acting formulation of brexpiprazole which, in in vivo studies, demonstrated therapeutic blood levels over a period of three months.

MTX110

·Demonstration, in vitro, of the potency of MTX110 in four patient-derived Glioblastoma cell lines.

FINANCIAL HIGHLIGHTS (including post period end)

·Total revenue in H1 2021 was £0.40m (1H20: £0.17m). Total revenue represents income from R&D collaborations plus grant revenue.

·Research and development costs decreased by 50% to £2.01m (1H20: £3.99m) as a result of the termination of MTD201 and focus on multiple earlier stage programmes.

·Administrative expenses decreased 44% to £1.64m (1H20: £2.93m) due to expenses incurred in connection with the Strategic Review and restructuring in the prior period.

·Net cash used in operating activities (after changes in working capital) in 1H21 was £3.11m, compared with £7.09m in 1H20.

·In July, post period end, the Company raised £10.0m before expenses in an UK Placing of 35.1m ordinary shares at £0.285 per share.

·The cash balance on 30 June 2021 was £4.20m.
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Commenting, Stephen Stamp, CEO and CFO of Midatech said: "We are pleased to report good progress throughout the Company and an expanded and exciting pipeline of programmes and opportunities. The disruption and costs of the restructuring in 2020 are now behind us. The first half of 2021 has been highly productive with three potentially viable Q-Sphera formulations, one internal and two for a collaboration partner. We believe the breakthrough data on the encapsulation of a protein could prove to be a very significant opportunity for Midatech."

The Company will be hosting a webinar at 5.30pm BST / 12.30pm EST on Monday 20 September 2021. The webinar is open to all existing and potential shareholders and those interested in attending may register via the following link where, following registration, they will be provided with access details:

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Participants may submit questions during the webinar or in advance via email to: [email protected]

This announcement contains inside information for the purposes of Article 7 of the Market Abuse Regulation (EU) 596/2014 as it forms part of UK domestic law by virtue of the European Union (Withdrawal) Act 2018 ("MAR"), and is disclosed in accordance with the company’s obligations under Article 17 of MAR.