On July 12, 2023 Pharmaxis Ltd (ASX: PXS) reported details of a final interim analysis of data from 10 patients who have completed 6 months’ treatment with PXS‐5505 in an open label phase 2 clinical trial in patients with the bone marrow cancer myelofibrosis (Press release, Pharmaxis, JUL 12, 2023, View Source;utm_campaign=Final%20set%20of%20interim%20data%20from%20PXS-5505%20trial%20in%20patients%20with%20MF&utm_content=Final%20set%20of%20interim%20data%20from%20PXS-5505%20trial%20in%20patients%20with%20MF+CID_f4f969d97c9cee20a80ec95d7772c8bb&utm_source=Campaign%20Monitor&utm_term=View%20Full%20Media%20Release [SID1234633179]). The phase 2 trial known as MF‐101 aims to demonstrate that PXS‐5505, an inhibitor of all lysyl oxidase enzymes (LOX), is safe and effective as a monotherapy in myelofibrosis patients who are intolerant, unresponsive or ineligible for treatment with approved JAK inhibitor drugs. These patients have very limited treatment options and a life expectancy of approximately 1 year1.

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A total of 21 patients have been enrolled in the cohort expansion phase of the study with 10 patients having completed 24 weeks of treatment. PXS‐5505 has shown to be well tolerated, with no serious treatment related adverse events reported, and has promising signs of clinical efficacy including improved symptom scores, stable or improved hematological parameters and reduced bone marrow fibrosis. 10 patients have dropped out of the study due to a lack of clinical response or adverse events unrelated to the drug.

Of the 10 patients completing 6 months treatment:
 5/9 evaluable patients2 had improved bone marrow fibrosis scores of ≥1 grade with 4 out of 5 fibrosis responders demonstrating stable hematological parameters and 3 out of 5 patients reporting symptomatic improvement

 4 had an improvement in symptom score of >20%

 7 had stable/improved hemoglobin (Hb) counts

 8 had stable/improved platelet counts of which 3 patients had Grade 4 (potentially life‐ threatening) thrombocytopenia at baseline

 No spleen volume response (SVR35) was identified

Dr. Lucia Masarova, Assistant Professor, Department of Leukemia at MD Anderson Cancer Center, Houston said, "PXS‐5505 continues to show not only an excellent safety profile but also promising clinical activity. The effect on bone marrow fibrosis is particularly exciting for a disease like myelofibrosis, where despite numerous years of research, we do not have any effective anti‐fibrotic drugs. It is encouraging to see that majority of 10 patients who completed 24 weeks of therapy also had improvements of symptoms and more importantly, stable or improved blood counts; including in those patients with severe thrombocytopenia.

"These results support plans to continue clinical investigation of the agent, including combinations with JAK inhibitors where the lack of overlapping hematological toxicity would make PXS‐5505 an ideal add‐on candidate."

The final results from this cohort will be submitted for presentation at the American Society of Haematology conference later this year. "Pharmaxis is the only company with pan‐LOX inhibitors in clinical development," said Pharmaxis CEO Mr Gary Phillips.

"The results from this trial with an oral LOX inhibitor showing significant improvements in fibrosis grade in bone marrow biopsies corroborate the findings of the trial of our topical LOX inhibitor in established skin scars where we saw a 30% reduction in collagen in skin biopsies after only 3 months treatment. Further to the published pre‐clinical research showing disease modification in several different indications, this is a mechanism which is now proven to be anti‐fibrotic in patients."

Mr Phillips continued, "The excellent safety profile of PXS‐5505 makes it an ideal candidate to combine with JAK inhibitors, the current standard of care in myelofibrosis. We anticipate that the impact on bone marrow fibrosis and other clinical parameters from the antifibrotic and intracellular effects of LOX inhibition should lead to improved outcomes for patients. We look forward to FDA feedback on our protocol and expect to start recruitment of this next cohort later this year."

Pharmaxis will host an investor briefing at 11.00am today, 12 July 2023, to discuss the interim data. Join the briefing at View Source;erS0mNkhUJfjiITg.

A recording will be uploaded to the Pharmaxis Investor Centre after the call at View Source;centre/investor‐briefing/.

Stockholm, Sweden & Turku, Finland – July 11, 2023 – 1stOncology/BioSeeker Group AB, a top 10 global pharma analytic provider, and OncoBone Ltd, a specialist in oncology and bone diseases, jointly announce the publication of “Insights into immuno-oncology drug development landscape with focus on bone metastasis” in the journal Frontiers in Immunology (Impact Factor 7.3).

This peer-reviewed article provides important timely insights to new and emerging immunotherapies with evidence for effects on bone metastases. Bone is among the main sites of metastasis in breast, prostate and other major cancers. However, bone metastases remain incurable causing high mortality, severe skeletal-related effects and decreased quality of life.

In order to provide an insight into the current immuno-oncology drug development landscape, 1stOncology, an award-winning cancer drug development resource, was used to identify 24 novel immunotherapies in preclinical or clinical development for breast and prostate cancer with data available on bone metastasis.

“We have previously performed searches for clinical studies including patients with bone metastases in immunotherapy trials and have concluded that the number of peer-reviewed publications in this area is very low” said Dr. Tiina Kähkönen, Chief Scientific Officer at OncoBone

“… considering the importance of this topic and knowing there are opportunities in development, we turned to an expanded data search using 1stOncology for finding therapies with data available for bone metastasis from more abundant information sources such as news, patents and meeting abstracts that include the latest published data available with a dramatic difference in the number of search results” Dr. Kähkönen added.

This review summarizes data available for the 24 identified novel immunotherapies. The data reveals how bone metastases can be approached using different modalities and the tumor microenvironment in bone provides many potential targets in immune, bone and tumor cells. Three of the identified therapies were considered to be especially promising as their targets are related to tumor growing in bone metastatic microenvironment and their clinical evaluation followed outcomes in bone metastatic patients with relevant outcome measurements.

“Considering that bone metastases are a high unmet medical need, it is surprising how few relevant studies finally address the efficacy of novel therapies on bone metastases either in preclinical or clinical studies” said Dr. Jussi Halleen, Chief Executive Officer at OncoBone.

“We are very pleased to see that 1stOncology could be such a substantial resource to dramatically improve the identification of immuno-oncology drug development related to bone metastasis and so rapidly provide the necessary data for this timely and very up to date publication” said Dr. Ronnie Andersson, Chief Scientific Officer at 1stOncology/BioSeeker Group.

With the recent emergence of osteoimmuno-oncology (OIO), a concept that emphasizes the significance of interactions between tumor, immune and bone cells in promoting tumor growth in bone metastasis, more therapeutic opportunities that primarily target bone metastasis are expected in the future.

The Frontiers in Immunology paper is titled “Insights into immuno-oncology drug development landscape with focus on bone metastasis” and can be accessed here.

About 1stOncology

1stOncology™ is an award-winning, market leading drug intelligence solution driving discovery of new opportunities in cancer drug development. Our mission is to deliver a superior intelligence service to cancer drug stakeholders and to make 1stOncology the go-to solution for those who are serious about their investment in oncology.

For more information about 1stOncology, visit https://www.1stoncology.com/awards

About BioSeeker Group

BioSeeker Group, founded in 1999 with offices in both Europe (Stockholm, Sweden) and the US (Boston, MA), helps stakeholders in cancer drug development and cancer care achieve excellence in drug development and treatment acumen through expert network (KOLs), data integration and technology solutions (artificial intelligence/machine learning) in our award-winning 1stOncology platform. For more information, please visit https://www.bioseeker.com

About OncoBone

OncoBone offers scientific expertise to pharmaceutical and biotech industry and their service providers globally, with key areas of operations in oncology and bone diseases, and bone metastasis as a unique field of expertise. For more information, please visit https://oncobone.com/

For further information please contact: BioSeeker Group AB Tel: +46-8-6731700 E-mail: [email protected] Our Offices: Stockholm, Sweden | Boston, MA USA   Newsletter & Market Alerts – Whitepapers – Awards – Publications – Testimonials – Twitter – LinkedIn

 

On July 11, 2023 Zhejiang Doer Biologics Co., Ltd. ("Doer Bio"), a clinical stage biopharmaceutical company developing innovative biotherapeutics for metabolic diseases and cancers, reported that it has entered into a license agreement with BioNTech SE (Press release, Doer Biologics, JUL 11, 2023, View Source [SID1234656212]).

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Under the terms of the agreement, Doer Bio will grant BioNTech a worldwide license to utilize one of Doer Bio’s innovative discoveries to research, develop, manufacture, and commercialize innovative biotherapeutics against an undisclosed target. Doer Bio will receive an upfront payment and will be eligible for potential development, regulatory, and commercial milestone payments.

"This license agreement with BioNTech is a great demonstration of the enormous potential of Doer Bio’s platform technologies, which has been well validated by extensive preclinical research and ongoing clinical studies," said Yanshan Huang, Ph.D., founder and Chief Executive Officer of Doer Bio.

"We are thrilled to work with BioNTech, a globally leading biopharmaceutical company, to translate our technologies and discoveries into novel therapies. We are looking forward to working with BioNTech to advance this innovation into clinic and ultimately benefit patients worldwide," commented Yongliang Fang, Ph.D., Chief Operating Officer of Doer Bio.

On July 11, 2023 ADC Therapeutics reported a voluntary pause in the enrollment of new patients in the Phase 2 LOTIS-9 clinical trial (ClinicalTrials.gov Identifier: NCT05144009) evaluating ZYNLONTA (loncastuximab tesirine-lpyl) and rituximab (Lonca-R) in unfit or frail patients with previously untreated diffuse large B-cell lymphoma (DLBCL) (Press release, ADC Therapeutics, JUL 11, 2023, View Source [SID1234634580]).

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The voluntary action was taken by the Company after a recent review of aggregate data of the 40 patients enrolled in the trial and consultation with the Data Monitoring Committee (DMC) which signaled potentially excessive respiratory-related events. These respiratory-related treatment-emergent adverse events (TEAEs) included seven Grade 5 fatal events and five Grade 3 or Grade 4 respiratory-related TEAEs. As per investigator assessment, eleven of the twelve events (including six of the seven Grade 5 fatal events) were individually assessed as unlikely or unrelated to study drug. Four out of the five Grade 3 or Grade 4 events have since resolved and the patients have completed treatment per protocol. The cause of these events remains under further investigation.

All patients with fatal events had one or more significant active underlying respiratory and/or cardiac co-morbidities including severe chronic obstructive pulmonary disease (COPD), pulmonary edema, chronic bronchiectasis, idiopathic pulmonary fibrosis and recent COVID-19 infection and all were greater than or equal to 80 years of age. The mean age was 82.7 years and the mean number of days from the last dose to death was 51 days, with a range of 19 to 86 days. It is important to note that all twelve of the patients with Grade 3-5 TEAEs in the LOTIS-9 study would have been excluded from the LOTIS-5 trial.

The Company’s decision to pause enrollment enables time to evaluate data around the TEAEs and determine next steps. The Company has notified all study investigators and regulatory authorities including the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) of the Company’s decision to pause enrollment. The Company does not expect to report additional data from the trial by the end of the year.

"Our top priority is the safety of every patient who participates in our clinical trials," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "Given the aggregate of the respiratory-related events seen in the trial, we implemented a voluntary pause of enrollment to allow for a thorough investigation of the data set. This trial includes a very difficult-to-treat patient population with limited treatment options, and we will provide an update on next steps when available."

LOTIS-9 Baseline Characteristics, Safety and Efficacy (as of May 10, 2023 data cutoff)

The tables below illustrate preliminary data from the LOTIS-9 clinical trial with a data cut-off date of May 10, 2023. These data are reflective of the 30 patients who were enrolled by that point; since this time an additional 10 patients have enrolled and received treatment as part of the study.

On July 11, 2023 BeiGene reported that on July 10, 2023 BeiGene and Novartis entered into a Mutual Termination and Release Agreement (the "Termination Agreement") to mutually terminate the Option Agreement, effective immediately (Filing, BeiGene, JUL 11, 2023, View Source [SID1234633334]). Pursuant to the Termination Agreement, BeiGene Switzerland regained full, global rights to develop, manufacture and commercialize ociperlimab.

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The foregoing description of the terms of the Termination Agreement does not purport to be complete and is qualified in its entirety by reference to the full text of the Termination Agreement, which the Company intends to file as an exhibit to a subsequent periodic report or on an amendment to this Current Report on Form 8-K.

Item 8.01. Other Events.
The Company will continue the enrollment of the Phase 3 AdvanTIG 302 trial of ociperlimab in combination with its anti-PD-1 antibody tislelizumab for the first-line treatment of patients with locally advanced, unresectable, or metastatic non-small cell lung cancer ("NSCLC") whose tumors exhibit high PD-L1 expression and do not harbor EGFR-sensitizing mutations or ALK translocations. Due to the changing treatment paradigm, the Company will discontinue the Phase 3 AdvanTIG 301 trial of ociperlimab in combination with tislelizumab versus durvalumab following concurrent chemoradiotherapy in patients with stage III unresectable NSCLC. The Company will carefully evaluate all available data to inform future development opportunities with ociperlimab.