On August 26, 2020 Novartis reported that, at primary analysis, the Phase III ASCEMBL study met its primary endpoint of statistically significant superiority in major molecular response (MMR) rate at 24 weeks for asciminib (ABL001) vs. bosutinib1 (Press release, Novartis, AUG 26, 2020, View Source [SID1234564031]). The study evaluates asciminib – a novel investigational treatment specifically targeting the ABL myristoyl pocket (STAMP) – in adult patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine-kinase inhibitors (TKIs)1. Patients with failure or intolerance to the most recently administered TKI therapy were included in the trial1.

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"Our ability to treat patients with TKIs changed CML care forever. However, the risk of disease progression is a reality for many patients – especially those who experience resistance to sequential TKI therapy or those who cannot adhere to treatment due to the daily impact of intolerable side effects16," said John Tsai, MD, Head of Global Drug Development and Chief Medical Officer, Novartis. "We are incredibly grateful to the patients and investigators around the world who participated in this study. These results with asciminib are a testament to our commitment to further transform CML care – this time through STAMP inhibition, by exploiting a natural regulatory mechanism of the ABL kinase."

Data from the ASCEMBL trial will be submitted for presentation at an upcoming medical meeting, and results will be shared with regulatory authorities. The U.S. Food and Drug Administration (FDA) has granted Fast Track designation for asciminib.

Findings from earlier studies of asciminib were presented during past annual meetings of the European Hematology Association (EHA) (Free EHA Whitepaper), and some details can be found here13,14.

About asciminib (ABL001)
Asciminib (ABL001) is an investigational treatment specifically targeting the ABL myristoyl pocket (STAMP). As a STAMP inhibitor, asciminib may help address tyrosine-kinase inhibitor (TKI)-resistance and intolerance in later treatment lines of chronic myeloid leukemia (CML)8-14, and it is being studied in several clinical trials in hopes of helping patients across multiple treatment lines of CML7,10,11,13-15,17.

About ASCEMBL
ASCEMBL is a Phase III, multicenter, open-label, randomized study comparing the oral investigational treatment asciminib (ABL001) versus bosutinib in patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase (Ph+ CML-CP) previously treated with two or more tyrosine-kinase inhibitors (TKIs)1. Patients with failure or intolerance to the most recently administered TKI therapy were included in the trial1.

About Novartis Commitment to CML
Our ongoing research in Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) has helped transform the disease from a fatal leukemia to a chronic condition in most patients. Novartis maintains an unwavering commitment to scientific innovation and access to care for patients worldwide. As an organization committed to patients, Novartis continues to reimagine CML care by pursuing ambitious goals with courage, passion and commitment for the global CML community.

On August 26, 2020 Cellesce reported that a new paper exploring the application of patient-derived organoids (PDOs) in the study of novel inhibitors of stem cell activity has recently been published in the journal PLOS ONE (Badder et al., 2020) (Press release, Cellesce, AUG 26, 2020, View Source [SID1234564030]).

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The study utilised 3D image-based morphometric analysis to quantify over 600 different features from individual organoids following treatment with TNKSi. While the morphometric analysis approach mirrored the trend seen in traditional biochemical assays, importantly this more sophisticated method was able to detect subtle alterations in growth and morphology in response to TNKSi with much greater accuracy. This leads to the conclusion that whilst traditional biochemical assays still have value in detecting compounds that merit further investigation in early stage drug discovery, combining these with 3D morphological analysis could be the key to unlocking the full potential of organoids in predictive drug testing at a much larger scale.

The study was led by Cellesce founding director Professor Trevor Dale’s Cardiff University-based academic research group working together with Cellesce and other partners. It describes the derivation of a novel set of colorectal cancer PDOs. The PDO models are then used as a platform to test the response of colorectal cancer to Wnt pathway modulation using small molecule inhibitors of the tankyrase protein (TNKSi). The work utilises a range of analysis techniques and highlights 3D quantitative image analysis in particular as having the potential to greatly enhance the high throughput prediction of compound efficacy in pre-clinical testing.

In recent years, there has been a shift within the drug discovery industry to focus on the development of compounds targeting ‘cancer stem cell’ populations within tumours. Historically, conventional chemotherapeutics have aimed to target the tumour bulk, to kill as many tumour cells as possible; the effects of which are usually to drive tumour regression in the short-term, albeit with greater side-effects – and a high chance of patient relapse. It is now widely understood that, in order to permanently prevent tumour growth, the initiating cancer stem cell population must be removed or inhibited. In the patient, this might have a relatively small impact initially on overall tumour size, but a longer term more effective treatment caused not by killing the cells, but by a more subtle change in the behaviour of the cells within the tumour.

The study of such targeted compounds has led to demand for better predictive model systems. While historical drug discovery has relied heavily on the predictive power of 2D cancer cell lines, their lack of cellular heterogeneity and relevant phenotypic behaviour leaves them largely unsuited for the study of cancer stem cell inhibitors, and far from ideally placed for anti-cancer drug development in general.

PDOs – which retain intra-tumoral complexity and, crucially, stem cell function – are now gaining increasing momentum as predictive in vitro models in the drug discovery field, with the potential to reduce compound attrition rates and development costs, ultimately increasing the number of successful compounds available for use in the clinic. A more complex model, the study argues, demands a more comprehensive method of analysis that is capable of capturing the complete range of changes that may occur in response to treatment.

The organoid lines generated for this study are licensed for sale by Cellesce in large scale validated batches produced using Cellesce’s patented bioprocess. Cellesce PDOs:

Are vialled ready for plating straight into the desired format
Come with full protocols and technical support
A custom expansion service is available with:
Culture optimisation and banking options
Large scale expansion with custom vialling
Cellesce has produced an Application Note that summarises the paper’s findings.

On August 26, 2020 InDex Pharmaceuticals Holding AB (publ) reported that interim report January – June 2020 (Press release, InDex Pharmaceuticals, AUG 26, 2020, View Source [SID1234564029])

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Focus on phase III preparations

"The commercial preparations have confirmed our belief in the potential of cobitolimod, where we estimate that the annual sales at a successful commercialisation can reach more than USD 1 billion," says Peter Zerhouni, CEO of InDex Pharmaceuticals.

Period April – June 2020

Net sales amounted to SEK 0.0 (0.0) million
Operating loss amounted to SEK –15.6 (–17.7) million
Result after tax amounted to SEK –15.6 (–17.7) million, corresponding to SEK –0.17 per share (–0.26) before and after dilution
Cash flow from operating activities amounted to SEK –32.8 (–13.6) million
Period January – June 2020

Revenues amounted to SEK 0.0 (0.0) million
Operating result amounted to SEK –39.6 (–34.9) million
Result after tax amounted to SEK –39.6 (–34.9) million, corresponding to SEK –0.45 per share (–0.51) before and after dilution
Cash flow from operating activities amounted to SEK –54.7 (–32.0) million
Cash and cash equivalents at the end of the period amounted to SEK 70.6 (50.5) million
Number of employees at the end of the period was 7 (7)
Number of shares at the end of the period was 88,781,275
All comparative amounts in brackets refer to the outcome during the corresponding period 2019.

Significant events during April – June 2020

InDex received positive responses from FDA and EMA regarding phase III development of cobitolimod for the treatment of moderate to severe ulcerative colitis
The annual general meeting in InDex Pharmaceuticals Holding AB was held on Monday April 20, 2020. Board members Wenche Rolfsen (also chairman), Uli Hacksell, Lennart Hansson and Stig Lökke Pedersen were re-elected, and Marlene Forsell and Yilmaz Mahshid were elected as new ordinary board members
Significant events after the reporting period

No significant events have occurred after the end of the reporting period
Other events

InDex announced that the successful results of the CONDUCT study will be presented orally at two leading medical conferences
CEO statement
Our focus remains on the phase III preparations with cobitolimod in ulcerative colitis. To assist, we have expanded our circle of medical advisors by setting up a North American advisory board. It is fantastic that we have succeeded to attract six of the top clinical experts in inflammatory bowel disease to support the continued development and positioning of cobitolimod with a focus on the US market. The group’s first meeting in June clearly showed that they see a potential prominent role for cobitolimod in the future treatment of ulcerative colitis. We continue the work to finalize the phase III design and the associated financing. Contingent on how the Covid-19 pandemic evolves, we plan to start the study in the second quarter of 2021.

We have also had a US consultancy firm to detail the positioning as a complement to the market research we conducted during the first quarter of this year, which has provided us with a deeper understanding of the future market. The commercial preparations have confirmed our belief in the potential of cobitolimod, where we estimate that the annual sales at a successful commercialisation can reach more than USD 1 billion. More than 2 million people have ulcerative colitis in the US, Europe and Japan, and of these about 60 percent are estimated to suffer from moderate to severe ulcerative colitis. Approximately 55 percent of this group are considered to have left-sided colitis and more than half do not respond to conventional treatment and need other alternatives. With an assumed price in the US, Europe and Japan in line with the most recently launched products, it corresponds to an addressable market for moderate to severe left-sided ulcerative colitis of over USD 9 billion annually.

Since May, there have been several important news regarding competing development projects in phase III in ulcerative colitis. One project has been discontinued and others have reported less promising clinical results. Several of these drug candidates will probably not reach the market in the end. Cobitolimod has a completely different mechanism of action and safety profile than these substances, and for InDex the news mainly mean reduced future competition. It will also be very interesting to get more data from these studies that we can learn from for our own development.

Our phase IIb results from the CONDUCT study will be presented orally in October at two leading gastroenterology conferences; the UEGW in Europe and the ACG in the US. These events are great opportunities for us to further reach the international scientific community with the successful results, as well as potential partners and specialist investors.

It is very inspiring with the support from all our medical advisors. They point out cobitolimod’s unique combination of efficacy and safety as well as the novel mechanism of action. I look forward to an eventful autumn for InDex with the continued phase III preparations.

Publication
This information is information that InDex Pharmaceuticals Holding AB (publ) is obliged to make public pursuant to the EU Market Abuse Regulation (MAR). The information was

On August 26, 2020 Oncopeptides reported interim result Q2 2020 (Press release, Oncopeptides, AUG 26, 2020, View Source [SID1234564028])

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Financial overview April 1 – June 30, 2020
Net sales amounted to SEK 0.0 M (0.0)
Loss for the period was SEK 401.0 M (loss: 171.9)
Loss per share, before and after dilution, was SEK 6.79 (loss: 3.52)
On June 30 cash and cash equivalents amounted to SEK 937.8 M (626.8)
Significant events during the period April 1 – June 30, 2020
Marty J Duvall was appointed CEO from July 1, and Jakob Lindberg assumed the role as
Chief Scientific Officer
NDA for accelerated approval of melflufen in the U.S was submitted
A laboratory for preclinical development was taken over to strengthen the technology platform and build the company’s pipeline
A directed share issue of SEK 1,414 M (USD 144 M) (before issue costs) to well-known life science investors, out of which SEK 716.4 M (before issue costs) was paid in after the end of the reporting period was completed
Enrollment in the OCEAN phase 3 study continues after the initial recruitment goal of 450 patients was reached in May
Final data from the pivotal HORIZON study were presented at EHA (Free EHA Whitepaper)
Patient enrollment to the company’s exploratory clinical studies was resumed in May after a temporary pause due to the COVID-19 pandemic
Significant events after the reporting period
The first patient was enrolled in the phase 1/2 AL-Amyloidosis study. This is the first study with melflufen in an indication outside multiple myeloma
Oncopeptides started a phase 2 study called PORT to evaluate an alternative administration of melflufen
Financial overview of the group

Conference call for investors, analysts and the media
The Interim Report Q2 2020 and an operational update will be presented by CEO Marty J Duvall and members of Oncopeptides management team, Wednesday August 26, 2020 at 14:00 (CET). The conference call will also be streamed via a link on the website: www. oncopeptides.com.

Financial calendar
Interim Report Q3, 2020: November 19, 2020
Year-end Report 2020: February 18, 2021
Interim Report Q1 2021: May 26, 2021
Annual General Meeting 2021: May 26, 2021

This information is information that Oncopeptides is obliged to make public pursuant to the EU Market Abuse Regulation and the Securities Markets Act. The information was submitted for publication, through the agency of the contact persons set out above, at 08:00 CET on August 26, 2020.

On August 26, 2020 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the results of non-clinical research on STA551, a Switch Antibody created by Chugai and currently in phase I clinical trial for solid tumors, have been published in Cancer Discovery Online (Press release, Chugai, AUG 26, 2020, View Source [SID1234564027]). Cancer Discovery, a journal of the American Association for Cancer Research (AACR) (Free AACR Whitepaper), is recognized as the world’s leading journal for reporting novel non-clinical and clinical research in the oncology field.

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"Antibody to CD137 activated by extracellular adenosine triphosphate is tumor selective and broadly effective in vivo without systemic immune activation"
(View Source)

The following points were demonstrated in this research:

Creation of STA551, an anti-CD137 agonist antibody that binds to CD137 in an adenosine triphosphate (ATP)-dependent manner and exerts agonistic activity, which is known to be present at high concentrations in solid tumor tissues.
STA551 binds to CD137 and activates T cells in the presence of ATP, but not in the absence of ATP (in vitro)
STA551 showed antitumor efficacy in all eight mouse models transplanted with multiple cancer cell lines (mouse)
Conventional anti-CD137 agonist antibody induces systemic immune reactions, but not with STA551 (mouse)
STA551 was well tolerated in animal toxicity studies
"We are very pleased that the results of our basic research on STA551, the first clinical development project to apply our Switch-Ig technology, were published in Cancer Discovery. We believe that the publication of the article was highly regarded not only for the non-clinical results of STA551 but also for the concept of Switch Antibody, which "binds to antigens only in the presence of a molecule (switch molecule) that are specifically present in pathological tissues," said Dr. Hisafumi Okabe, Executive Vice President, Supervisory responsibility for Research and Translational Research. "We are confident that Chugai’s strength in antibody engineering technology will not only solve the challenges of conventional antibody drugs but also further expand the potential of antibody drugs as a modality. We are very much looking forward to the ongoing phase I clinical trial of STA551 to show a high safety profile and anti-tumor efficacy and become a drug that can contribute to the treatment of patients."

Aiming to become a top innovator in the healthcare industry, Chugai strives to contribute to patients around the world by providing innovative medicines and services through the pursuit of science and unique technological capabilities.

About STA551
STA551 is a Switch Antibody using Switch-Ig developed by Chugai. It activates by recognizing adenosine triphosphate (ATP) as a switch molecule, which is believed to exist in high concentration in tumor tissues, and binds to the target antigen, CD137. A phase I clinical trial for solid tumors is ongoing.

About Switch-Ig
Switch-Ig is a technology that enhances the disease site specificity of antibodies. Conventional antibodies may bind to the target antigen not only in the disease site but also in normal tissues, causing problems such as side effects. Switch-Ig is an antibody designed to bind to a target antigen only in the presence of a molecule (switch molecule) that becomes highly concentrated at the disease site. It is less likely to react with the target antigen in normal tissues with low switch molecule concentrations. By utilizing this technology, it is expected that the antibody can react specifically to the disease site and avoid the safety problems and deterioration of plasma kinetics caused by binding to normal tissues.