On November 7, 2023 Race Oncology (ASX:RAC) reported positive interim clinical results from an ongoing investigator-initiated Phase II study of its core asset bisantrene in combination with fludarabine and clofarabine in R/R AML patients (Press release, Race Oncology, NOV 7, 2023, View Source [SID1234637060]).

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The trial abstract has been peer-reviewed and the interim results selected for presentation at the prestigious American Society of Hematology (ASH) (Free ASH Whitepaper) 65th Annual Conference in December.

The oral poster presentation titled Bisantrene in combination with fludarabine and clofarabine as salvage therapy for adult patients with relapsed or refractory acute myeloid leukemia (AML) – an open-label, phase II study describes clinical results from the first 15 evaluable patients treated on study since August 2021.

Bisantrene is a unique product that is a small molecule, anthracene-based chemotherapeutic that has anti-cancer benefits but additionally reduced cardiotoxicity, meaning it is less likely to cause heart dysfunction.

In combination with fludarabine and clofarabine, bisantrene administered over four days induced a clinical response in 6 of 15 evaluable patients (40%) with a median age of 48 (range 19-69) with advanced (R/R AML).

Five of the six treatment-responsive patients were well enough to receive a potentially curative bone marrow transplant within one to three months of treatment.

Of the five-bone marrow transplanted patients, three have since died with one from graft-versus-host disease, another relapsed within four months of transplant, and the third from infection after two years. The two other patients remain disease free and in complete remission.

Palliative patients responding ‘quite frankly amazing’
RAC executive director Dr Pete Smith says AML patients who fail many lines of treatment are likely to be only offered palliative care as many clinicians believe the risks of using more experimental treatments exceed the chance of the patient responding.

He says many clinicians would consider even a single patient being able to be bridged to a bone marrow transplant a success in such a heavily pre-treated population.

"This is a patient group that normally would not be treated in Australia and clinicians would have given up by now," Smith says.

"They have failed an average of four lines of therapy, so they tried some drug or drug combination then maybe had a response but stopped responding then went on something else."

Smith says outlook for the patients in the trial without treatment was "dire" with a life expectancy measured in weeks if they do not receive efficacious treatment.

He says to take this patient population and put them on the bisantrene drug combination and see it relatively well tolerated and 40% responding with five having a complete response is "quite frankly amazing".

‘Very encouraging results in younger AML patients’
The trial is running at the Sheba Medical Centre in Israel, under the supervision of key opinion leader Professor Arnon Nagler.

"These rather impressive results in such a heavily pre-treated population support further studies of bisantrene-based combinations, including those with venetoclax or hypomethylating agents," Nagler says in the trial abstract.

Calvary Mater Newcastle and John Hunter Hospitals director of haematology Professor Dr Anoop Enjeti, who was not involved in the study, says it "produced very encouraging results in younger AML patients".

"Many of these patients achieved a complete or a partial remission, enabling a significant proportion to go on to a bone marrow transplant," he says.

"These impressive results provide proof of concept supporting further trials of bisantrene in combination with other AML treatments to improve outcomes for this leukaemia."

Moving bisantrene into less advanced AML patients
Smith says the positive trial data will help progress bisantrene as a treatment for patients that are more likely to respond.

"All new oncology drugs and drug combinations start out in the hardest to treat patients with the most advanced disease.

"As clinical understanding grows around a drug’s efficacy and side-effects, clinicians will start to use the drug in earlier-stage patients who are more likely to respond to treatment."

Furthermore, he says the positive clinical trial data is the foundation of commercialisation or partnership discussions with large pharmaceutical companies.

"Race continues to engage with potential pharma partners and will update the market on progress when appropriate," he says.

"It’s still early days in terms of digesting this data and working out the path forward but very encouraging."

On November 7, 2023 Clarity Pharmaceuticals (ASX: CU6) ("Clarity"), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, reported that 50 patients have now been imaged with 64Cu-SAR-Bombesin in its United States-based diagnostic trial, SABRE (NCT05407311)1, for participants with PSMA-negative prostate cancer (Press release, Clarity Pharmaceuticals, NOV 7, 2023, View Source [SID1234637015]).

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SABRE, which derives from "Copper-64 SAR-Bombesin in Biochemical Recurrence of prostate cancer" is a Phase II Positron Emission Tomography (PET) imaging trial of participants with PSMA-negative biochemical recurrence (BCR) of prostate cancer following definitive therapy. It is a multi-centre, single arm, non-randomised, open-label trial of 64Cu-labelled SAR-Bombesin. The primary objectives of the trial are to investigate the safety and tolerability of the product as well as its ability to correctly detect recurrence of prostate cancer.

Andrei Iagaru, MD, the Lead Principal Investigator for the trial, commented, "We are very excited to have successfully imaged 50 participants in the SABRE trial which further explores the clinical benefits of the innovative SAR-Bombesin product. Preclinical and clinical findings thus far indicate that SAR-Bombesin holds significant potential for improving the diagnosis and treatment of prostate cancer, giving hope to clinicians and patients who have no other suitable diagnostic options available. Being able to now visualise the gastrin-releasing peptide receptor (GRPr) expressing lesions with SAR-Bombesin has the potential to change the entire treatment paradigm for patients. With more tools to detect prostate cancer that may not be visible with other imaging agents, we may be able to better diagnose and offer more effective treatment for their disease.

"Unique to Clarity’s SAR Technology is the ability to image patients at later timepoints due to the optimal half-life of 64Cu. As such, 64Cu-SAR-Bombesin enables imaging not only on the day of product administration, but also at later timepoints, which may add utility to the diagnosis of cancerous lesions. We look forward to analysing data from the SABRE trial in hopes of continuing to validate the benefits associated with this agent and better managing the patients that have few options at present in the face of a devastating diagnosis."

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are pleased to have reached our recruitment target in our Phase II SABRE trial with the 64Cu-SAR-Bombesin imaging product. SAR-Bombesin has already resulted in improvements to the management of prostate cancer for patients with PSMA-negative or low PSMA expressing lesions through our clinical program. We believe this product has immense potential, both as a theranostic and as a stand-alone diagnostic, as it targets GRPr, which is present in a number of cancers, potentially broadening its use beyond PSMA-negative prostate cancer.

"The successful C-BOBCAT and BOP investigator-initiated trials have already showed the utility of SAR-Bombesin and its potential to identify disease in some patient subgroups where conventional diagnostic imaging has failed. We look forward to reporting further data relating to the potential advantages of SAR-Bombesin and, subject to these results, moving this product into a registrational Phase III trial."

About SAR-Bombesin
SAR-Bombesin is a highly targeted pan-cancer radiopharmaceutical with broad cancer application. It targets the gastrin-releasing peptide receptor (GRPr) present on cells of a range of cancers, including but not limited to prostate, breast and ovarian cancers. GRPr is found in up to 100% of prostate cancers, including prostate cancers that don’t express PSMA (PSMA-negative)2-6. The product utilises Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-Bombesin is a Targeted Copper Theranostic (TCT) that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu SAR-Bombesin and 67Cu SAR-Bombesin are unregistered products. Individual results may not represent the overall safety and efficacy of the products. The data outlined in this announcement has not been assessed by health authorities such as the US Food and Drug Administration (FDA). A clinical development program is currently underway to assess the efficacy and safety of these products. There is no guarantee that these products will become commercially available.

About Prostate Cancer
Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide7. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of prostate cancer in the US and around 34,700 deaths from the disease8.

Approximately 20% of prostate cancers with BCR are PSMA-PET negative9-12. These patients are therefore unlikely to respond to therapeutic PSMA-targeted products and currently have few treatment options available to them. Given the prostate cancer indication is one of the largest in oncology, there is a significant unmet medical need in this segment.

On November 6, 2023 Zetagen Therapeutics, a private, clinical-stage, biopharmaceutical company focused on driving breakthrough innovation in the treatment of metastatic cancers to bone and soft tissue organs as well as osteologic interventions, reported its approval from the Human Research Ethics Committee (HREC) of Australia to begin a pilot study using its novel therapy ZetaFuse bone graft for the treatment of cervical degenerative disc disease (Press release, Zetagen Therapeutics, NOV 6, 2023, View Source [SID1234647536]). The pilot study is a randomized, open-label, two-level cervical program which will examine the safety and efficacy of ZetaFuse bone graft in patients undergoing anterior cervical discectomy and fusion (ADCF) surgery.

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"We are pleased to begin this pilot study in Australia," said Joe C. Loy, CEO of Zetagen Therapeutics. "If successful, ZetaFuse will be another asset to our growing pipeline of therapies focused on serious osteologic issues ranging from lytic lesions in metastatic cancers to various skeletal related events."

"For patients living with cervical degenerative disc disease, ACDF surgery is an option to relieve pain and stabilize the spine," said Nikhil Thakur, MD, co-founder, and Chief Medical Officer of Zetagen Therapeutics. "Our hope is that by introducing ZetaFuse bone graft as part of the ACDF surgical procedure we can empower spine surgeons with a safe, osteoinductive treatment option."

ZetaFuse, is a synthetic, small-molecule, osteo-inductive biologic technology being developed to aid in bone healing of spinal fusions. It works through a mechanism of action (MOA) which is a novel and patented molecular pathway. When the pathway is activated, it stimulates stem cells, activating cells to grow healthy bone known as "osteoblasts", and inhibits cells associated with bone degradation called "osteoclasts", preventing bone resorption.

ZetaFuse was granted Breakthrough Device Designation status in 2021 from the U.S. Food and Drug Administration (FDA) for spinal fusion procedures including interbody fusion in the anterior cervical, thoracic, and lumbar spine or posterior fusions in the cervical, thoracic, and lumbar spine.

In the United States, interbody spinal fusion surgeries are the most commonly performed spinal procedures, stemming often from diagnoses of lumbar degenerative disc disease and cervical disc replacement. In the last 20 years, spinal fusion procedures have increased nearly two-fold, with an estimated 450,000 lumbar and 150,000 cervical spinal fusion procedures performed annually.[1]

The two year study will enroll 10 patients and be conducted at Prince of Wales Hospital and Prince of Wales Private Hospital in Australia.

[1] J Spine Surg 2020;6(4):752-761 | View Source

On November 6, 2023 JSR reported its consolidated Financial Results for the First Six Months of the Fiscal Year Ending March 31, 2024 (Press release, JSR, NOV 6, 2023, View Source [SID1234639228]).

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On November 6, 2023 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) and Dewpoint Therapeutics reported a strategic R&D collaboration to advance Dewpoint’s leading oncology pipeline programmes of condensate modifying therapeutics ("c-mods") to Investigational New Drug Applications ("INDs") using Evotec’s industry-leading fully integrated data-driven platform ("INDiGO") (Press release, Evotec, NOV 6, 2023, View Source [SID1234637134]).

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The partnership brings together Dewpoint’s advanced oncology pipeline programmes discovered using its groundbreaking condensate biology and A.I. technology platform for identifying modulators of biomolecular condensates with Evotec’s leading capabilities to de-risk and accelerate pre-clinical development candidates ("PDCs") to first-in-human ("FIH") clinical studies.

Under the collaboration, Evotec will facilitate the rapid development of Dewpoint’s oncology assets using Evotec’s fully integrated clinical-enabling INDiGO platform to de-risk and accelerate the path to clinical testing. The partnership also enables Dewpoint to maximise capital efficiency while reducing risk. The agreement is based on a risk-sharing arrangement followed by milestone and royalty payments to Evotec based on the success of the overall programmes.

Dr Matthias Evers, Chief Business Officer of Evotec, commented: "We are excited to enter this strategic development partnership with Dewpoint. Their innovative approach is based on a holistic understanding, which can significantly expand the target space across indications. By combining our complementary expertise, Evotec’s development platform will serve as the capital-efficient IND engine for this highly collaborative partnership. We look forward to working closely together with their team to make Dewpoint’s groundbreaking innovations available to patients."

"Dewpoint’s strategic partnership with Evotec leverages the world-class speed of their development platform to accelerate our oncology assets into the clinic. Evotec’s integrated state-of-the-art operational technologies have been proven to deliver high quality INDs across the industry. A strategic relationship of this nature significantly enhances our development capabilities which can be transformative for a company at our stage of development, and we are delighted to have been able to forge this partnership with a leader like Evotec," commented Ameet Nathwani, M.D., CEO at Dewpoint.

About Condensates
Condensates are membraneless organelles that form dynamically throughout the cell via a process called phase separation. These subcellular compartments organise and concentrate molecules within cells to enable certain key biochemical processes. The dysregulation of biomolecular condensates has been observed in many diseases, including cancer, diabetes and neurological disorders. Condensate-modifying drugs (c-mods) potentially provide novel therapeutic options for complex diseases and historically undruggable targets.