On September 9, 2019 AstraZeneca reported detailed results from the Phase III CASPIAN trial, showing Imfinzi (durvalumab) significantly improved overall survival (OS) in patients with previously-untreated extensive-stage small cell lung cancer (SCLC) (Press release, AstraZeneca, SEP 9, 2019, View Source [SID1234539373]).

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Imfinzi in combination with four cycles of standard-of-care (SoC) chemotherapy (etoposide with either cisplatin or carboplatin) demonstrated a statistically-significant and clinically-meaningful improvement in OS vs. SoC consisting of up to six cycles of chemotherapy and optional prophylactic cranial irradiation (PCI).

The risk of death was reduced by 27% (equal to a hazard ratio of 0.73), with median OS of 13.0 months for Imfinzi plus chemotherapy vs. 10.3 months for SoC. Results showed a prolonged OS benefit with an estimated 33.9% of patients alive at 18 months following treatment with Imfinzi plus chemotherapy vs. 24.7% of patients following SoC.

Across all efficacy endpoints, benefits were observed in patients treated with Imfinzi plus chemotherapy vs. SoC. Results showed a significantly higher progression-free survival (PFS) rate at 12 months (17.5% vs. 4.7%), a 10.3% increase in confirmed objective response rate (ORR) (67.9% vs. 57.6%), and improved duration of response (DOR) at 12 months (22.7% vs. 6.3%).

The results were presented at the Presidential Symposium of the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, Spain.

José Baselga, Executive Vice President, Oncology R&D said: "We are encouraged to see more than a third of small cell lung cancer patients treated with Imfinzi plus chemotherapy alive at the 18-month landmark, which is remarkable given the aggressive nature of the disease. It is also noteworthy that these results may enable physicians to choose Imfinzi in combination with either cisplatin or carboplatin chemotherapy backbones. We look forward to working with regulatory authorities to bring Imfinzi to patients with small cell lung cancer around the world as soon as possible."

Luis Paz-Ares, MD, Ph.D., Chair, Medical Oncology Department, Hospital Universitario Doce de Octubre, Madrid, Spain and principal investigator in the Phase III CASPIAN trial said: "Patients have had limited treatment options for small cell lung cancer, a devastating disease where the five-year survival rate has been as low as 6%. The significant survival benefit demonstrated with Imfinzi combined with only four cycles of a choice of chemotherapy compared to a robust control arm, provides evidence and hope of a new treatment option for these patients."

SCLC is an aggressive, fast-growing cancer that recurs and progresses rapidly despite initial response to platinum-based chemotherapy.1

i Etoposide plus investigator choice of cisplatin or carboplatin chemotherapy.

ii The data cut-off date for analysis of OS, PFS and ORR was 11 March 2019.

iii PFS was not formally tested for statistical significance.

iv Confirmed responses according to investigator assessment per RECIST v1.1.

The safety and tolerability of Imfinzi in combination with SoC etoposide and platinum-based chemotherapy was consistent with previous trials. Results showed that 61.5% of patients experienced a Grade 3 or 4 AE with Imfinzi plus SoC (all causes) vs. 62.4% with SoC, and patients discontinuing treatment due to AEs were similar between arms (9.4% vs. 9.4%).

Imfinzi is also being tested following concurrent chemoradiation therapy in limited-stage SCLC in the Phase III ADRIATIC trial.

Imfinzi is approved in the curative-intent setting of unresectable, Stage III non-small cell lung cancer after chemoradiotherapy in 49 countries, including the US, Japan and across the EU, based on the Phase III PACIFIC trial.

About CASPIAN

The CASPIAN trial is a randomised, open-label, multi-centre, global, Phase III trial in the 1st-line treatment of patients with extensive-stage SCLC. The trial compared Imfinzi in combination with etoposide and either cisplatin or carboplatin chemotherapy, or Imfinzi, tremelimumab and chemotherapy vs. chemotherapy alone. In the experimental arms, patients were treated with up to four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional PCI. The trial will continue to the final analysis of OS for the combination of Imfinzi, tremelimumab and chemotherapy.

The trial is being conducted in more than 200 centres across 22 countries, including in the US, Europe, South America, Asia and the Middle East. The primary endpoint is OS.

About small cell lung cancer

Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths.2 Lung cancer is broadly split into NSCLC and SCLC, with about 15% classified as SCLC.3 About three quarters of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body. Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.4

About Imfinzi

Imfinzi (durvalumab) 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.

Imfinzi is also approved for previously-treated patients with advanced bladder cancer in 10 countries, including the US.

As part of a broad development programme, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, small cell lung cancer, bladder cancer, head and neck cancer, liver cancer, cervical cancer, biliary tract cancer and other solid tumours.

About AstraZeneca in lung cancer

AstraZeneca has a comprehensive portfolio of approved and potential new medicines in late-stage clinical development for the treatment of different forms of lung cancer spanning several stages of disease, lines of therapy and modes of action. We aim to address the unmet needs of patients with EGFR-mutated tumours as a genetic driver of disease, which occur in 10-15% of NSCLC patients in the US and EU and 30-40% of NSCLC patients in Asia, with our approved medicines Iressa (gefitinib) and Tagrisso (osimertinib), and ongoing Phase III trials ADAURA, LAURA, FLAURA and FLAURA2 as well as the Phase II combination trials SAVANNAH and ORCHARD.5-7

Our extensive late-stage Immuno-Oncology programme focuses on lung cancer patients without a targetable genetic mutation which represents approximately three-quarters of all patients with lung cancer.8 Imfinzi (durvalumab), an anti-PDL1 antibody, is in development for patients with advanced disease (Phase III trials POSEIDON, PEARL, and CASPIAN) and for patients in earlier stages of disease including potentially-curative settings (Phase III trials AEGEAN, PACIFIC-2, ADRIATIC, ADJUVANT BR.31, PACIFIC-4, and PACIFIC-5) both as monotherapy and in combination with tremelimumab and/or chemotherapy.

About AstraZeneca’s approach to Immuno-Oncology (IO)

IO is a therapeutic approach designed to stimulate the body’s immune system to attack tumours. Our IO portfolio is anchored by immunotherapies that have been designed to overcome anti-tumour immune suppression. We believe that IO-based therapies offer the potential for life-changing cancer treatments for the clear majority of patients.

We are pursuing a comprehensive clinical-trial programme that includes Imfinzi (anti-PDL1) as monotherapy and in combination with tremelimumab (anti-CTLA4) in multiple tumour types, stages of disease, and lines of therapy, 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 our IO portfolio with radiation, chemotherapy, small targeted molecules from across our Oncology pipeline, and from our research partners, may provide new treatment options across a broad range of tumours.

About AstraZeneca in oncology

AstraZeneca has a deep-rooted heritage in oncology and offers a quickly-growing portfolio of new medicines that has the potential to transform patients’ lives and the Company’s future. With at least six new medicines to be launched between 2014 and 2020, and a broad pipeline of small molecules and biologics in development, the Company is committed to advance oncology as a key growth driver for AstraZeneca focused on lung, ovarian, breast and blood cancers. In addition to AstraZeneca’s main capabilities, the Company is actively pursuing innovative partnerships and investments that accelerate the delivery of our strategy, as illustrated by the investment in Acerta Pharma in haematology.

By harnessing the power of four scientific platforms – Immuno-Oncology, Tumour Drivers and Resistance, DNA Damage Response and Antibody Drug Conjugates – and by championing the development of personalised combinations, AstraZeneca has the vision to redefine cancer treatment and, one day, eliminate cancer as a cause of death.

On September 9, 2019 Nuvo Pharmaceuticals Inc. (Nuvo or the Company) (TSX:NRI;OTCQX:NRIFF), a Canadian focused, healthcare company with global reach and a diversified portfolio of commercial products, reported that Jesse Ledger, Nuvo’s President & Chief Executive Officer will present at the H.C. Wainwright 21st Annual Global Investment Conference to be held September 8-10, 2019 in New York City (Press release, Nuvo Pharmaceuticals, SEP 9, 2019, https://www.prnewswire.com/news-releases/nuvo-pharmaceuticals-update-to-nuvos-presentation-time-at-hc-wainwright-global-investment-conference-300913789.html [SID1234539389]).

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Updated Nuvo Presentation Details

Date:

Tuesday, September 10, 2019

Time:

4:15 p.m. ET (previously announced time 5:00 p.m. ET)

Location:

Lotte New York Palace Hotel

A link to the live audio webcast of the presentation will be available on the Home Page of the Company’s website at www.nuvopharmaceuticals.com. The archived webcast will be available for 30 days.

Mr. Ledger will be available during the conference for one-on-one meetings. Members of the investment community who are interested in meeting with the Company should contact conference coordinators to arrange an appointment or contact Nuvo directly via email at [email protected].

On September 9, 2019 Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) and BridgeBio Pharma, Inc.’s (NASDAQ:BBIO) subsidiary Eidos Therapeutics, Inc. (NASDAQ:EIDX) reported an agreement that grants Alexion an exclusive license to develop and commercialize AG10 in Japan. AG10 is a small molecule designed to treat the root cause of transthyretin amyloidosis (ATTR) – destabilized and misfolded transthyretin (TTR) protein – by binding and stabilizing TTR in the blood. Eidos is currently evaluating AG10 in a Phase 3 study in the U.S. and Europe for ATTR cardiomyopathy (ATTR-CM) – a progressive, fatal disease caused by the accumulation of misfolded TTR amyloid in the heart – and plans to begin a Phase 3 study in ATTR polyneuropathy (ATTR-PN) – a progressive, fatal disease caused by the accumulation of misfolded TTR amyloid in the peripheral nervous system.

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"There is a significant need for new treatments for TTR amyloidosis. We believe AG10 holds promise in its ability to stabilize TTR and halt disease progression," said John Orloff, M.D., Executive Vice President and Head of Research & Development at Alexion. "We are excited by the potential to grow our amyloidosis portfolio by partnering with Eidos to expand the development of AG10 to Japan. Alexion has more than 10 years of experience operating there, and we look forward to applying our expertise to bring AG10 to Japanese patients."

"The Phase 2 study in ATTR-CM suggested that AG10 has the potential to become an important treatment option for the underserved ATTR-CM population. The trial showed that AG10 was generally well-tolerated and resulted in near-complete stabilization of TTR, which is known to be correlated with disease severity in ATTR-CM. In the study, AG10 also normalized serum TTR levels, a prognostic indicator of survival in ATTR patients," said Jonathan Fox, M.D., Ph.D., President and Chief Medical Officer of Eidos. "We have now begun our Phase 3 program to evaluate the safety and efficacy of AG10 in larger studies. This agreement provides the potential opportunity to help even more patients globally by leveraging Alexion’s significant development and commercial experience to expand the AG10 program into Japan."

Under the terms of the agreement, Alexion will acquire an exclusive license for the clinical development and commercialization of AG10 in Japan. Eidos will receive an upfront payment of $25 million and an equity investment of $25 million at a premium to the market price upon deal execution, with the potential for additional Japanese-based milestone- and royalty-dependent payments.

About AG10

AG10 is an investigational, orally-administered small molecule designed to potently stabilize tetrameric transthyretin, or TTR, thereby halting at its outset the series of molecular events that give rise to TTR amyloidosis, or ATTR. In a Phase 2 clinical trial in patients with symptomatic ATTR-CM, AG10 was generally well tolerated, demonstrated greater than 90 percent average TTR stabilization at Day 28, and increased serum TTR concentrations, a prognostic indicator of survival in a retrospective study of ATTR-CM patients, in a dose-dependent manner.

AG10 was designed to mimic a naturally-occurring variant of the TTR gene (T119M) that is considered a rescue mutation because co-inheritance has been shown to prevent or ameliorate ATTR in individuals also inheriting a pathogenic, or disease-causing, mutation in the TTR gene. To our knowledge, AG10 is the only TTR stabilizer in development that has been observed to mimic the stabilizing structure of this rescue mutation.

The Phase 3 ATTRibute-CM study of AG10 in patients with ATTR-CM is underway in the United States and Europe. Part A of the study will assess the change from baseline in 6-minute walk distance (6MWD) at 12 months. Part B of the study will evaluate reduction in all-cause mortality and frequency of cardiovascular-related hospitalizations will be evaluated at 30 months. In addition, Eidos plans to initiate a Phase 3 study of AG10 in ATTR polyneuropathy (ATTR-PN) in the second half of 2019.

About Transthyretin Amyloidosis (ATTR)

There is significant medical need in transthyretin amyloidosis (ATTR) given the large patient population and an inadequate current standard of care. ATTR is caused by the destabilization of TTR due to inherited mutations or aging and is commonly divided into three distinct categories: wild-type ATTR cardiomyopathy (ATTRwt-CM), mutant ATTR cardiomyopathy (ATTRm-CM), and ATTR polyneuropathy (ATTR-PN). The worldwide prevalence of each disease is approximately 400,000 patients, 40,000 patients and 10,000 patients, respectively.

All three forms of ATTR are progressive and fatal. For patients with untreated ATTRwt-CM and ATTRm-CM, symptoms usually manifest later in life (age 50+), with median survival of three to five years from diagnosis. ATTR-PN either presents in a patient’s early 30s or later (age 50+), and results in a median life expectancy of five to ten years from diagnosis for untreated patients. Progression of all forms of ATTR causes significant morbidity, impacts productivity and quality of life, and creates a significant economic burden due to the costs associated with progressively greater patient needs for supportive care. (Press release, BridgeBio, SEP 9, 2019, View Source [SID1234576264])

On September 9, 2019 PharmaMar (MSE:PHM) reported new data on lurbinectedin during the World Conference on Lung Cancer (WCLC), which is taking place from 7th to 10th September in Barcelona (Press release, PharmaMar, SEP 9, 2019, View Source [SID1234539374]). The Conference, organized by the International Association for the Study of Lung Cancer (IASLC), brings together the world’s leading experts on this pathology and presents the latest advances in its treatment.

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At this conference, PharmaMar presented two posters on lurbinectedin for the treatment of Small Cell Lung Cancer (SCLC).

The first of them evaluates new combinations with lurbinectedin for the treatment of this type of tumor. The poster entitled "Lurbinectedin (L) Combined with Paclitaxel (P) or Irinotecan (I) in Relapsed SCLC. Results from Two Phase Ib Trials (Abstract 1588)" shows the results of a Phase Ib trial in which combinations of lurbinectedin with paclitaxel or irinotecan were evaluated in patients with relapsed SCLC. Both combinations have shown similar activity and a predictable and manageable safety profile. The combination of lurbinectedin and irinotecan has shown encouraging activity in the third line treatment of patients. Also of interest, the combination of lurbinectedin and paclitaxel has shown higher activity in resistant patients (CTFI<90 days – patients for whom time from the last dose of first-line chemotherapy to the occurrence of progressive disease is less than 90 days).
These results warrant further evaluation of the combinations of lurbinectedin with paclitaxel or irinotecan. The expansion cohort of the irinotecan combination is already ongoing.

The second poster, entitled "Antitumor Activity of Single Agent Lurbinectedin in Patients with Relapsed SCLC Occurring ≥30 Days After Last Platinum Dose (Abstract 1710)" shows data from SCLC cohort of the Phase II Basket trial of lurbinectedin as a single agent, (presented in an oral session at the last ASCO (Free ASCO Whitepaper) Congress). Data are shown for the subset of 84 patients with a CTFI≥30 (time from the last dose of first-line chemotherapy to the occurrence of progressive disease is longer than or equal to 30 days). In this group of patients, the Overall Response Rate (ORR) was 40.5%. For the resistant patients with a CTFI of 30-89 days, the ORR was 29.2%, for whom no currently approved treatment exists. For the 60 patients that were sensitive (CTFI≥90 days; patients for whom time from the last dose of first-line chemotherapy to the occurrence of progressive disease is longer than or equal to 90 days), the ORR was 45%.

As for the safety of the compound in this group of patients, lurbinectedin has shown a safety profile that was acceptable and well tolerated. The most common treatment-related adverse effect has been neutropenia, and no unexpected toxicities have been observed.

During the Congress, Dr. Camilla L. Christensen, from Harvard University, will present in an oral session on transcription as a target in the treatment of SCLC, where, among others, the mechanism of action of lurbinectedin will be discussed. Lurbinectedin is a selective inhibitor of the oncogenic transcription programs on which many tumors are particularly dependent.

On September 9, 2019 KAHR Medical, a biopharmaceutical company developing a novel drug platform based on bi-functional, immunotherapeutic fusion proteins known as DSP (Dual Signaling Proteins), reported a new clinical collaboration with Roche (Press release, KAHR Medical, SEP 9, 2019, View Source [SID1234539390]). The collaboration will explore KAHR’s lead program, DSP107, a SIRPα-41BBL DSP, in combination with Roche’s PD-L1-blocking checkpoint inhibitor (CPI) atezolizumab (Tecentriq) in patients with advanced NSCLC who are refractory to checkpoint inhibitors. KAHR expects to file an Investigational New Drug (IND) application with the U.S. Food Drug Administration (FDA) and begin a Phase I/II trial in H1 2020 to evaluate DSP107 as a monotherapy and in combination with atezolizumab.

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"We are extremely pleased to collaborate with Roche to study the potential of atezolizumab in combination with DSP107, our lead drug candidate," said Yaron Pereg, PhD, CEO, KAHR Medical. "The combined approach of DSP107 alongside immune-checkpoint inhibition has already shown promise in preclinical studies. We look forward to examining the potential of DSP107 with atezolizumab in treating NSCLC patients with limited treatment options."

DSP107 targets CD47-overexpressing tumors, simultaneously blocking macrophage inhibitory signals and delivering an immune costimulatory signal to tumor antigen-specific activated T-cells. CD47 is overexpressed on many cancer cells and binds SIRPα on immune phagocytic cells to produce a "don’t eat me" signal. DSP107 binds CD47 on cancer cells, blocking interaction with SIRPα and thus blocking the "don’t eat me signal". Simultaneously, DSP107 binds 41BB on T-cells, stimulating their activation. These activities lead to targeted immune activation through both macrophage and T-cell mediated tumor destruction. In combination with atezolizumab, DSP107 has the potential to enhance anti-tumor immune response.

The planned Phase I/II study will evaluate the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of DSP107 in advanced solid tumors. The preliminary efficacy of both DSP107 monotherapy and combination therapy with atezolizumab will be evaluated in patients with advanced NSCLC who are refractory to PD-1/PD-L1 inhibitors. KAHR will be the sponsor of the study and Roche will provide the clinical supply of atezolizumab.