On September 20, 2022 Telix Pharmaceuticals Limited (ASX: TLX, Telix, the Company) reported the final results from the IPAX-1 Ph I/II study of TLX101 therapy (4-L-[ 131I] iodo-phenylalanine, or 131I-IPA) in combination with external beam radiation therapy (EBRT) in recurrent glioblastoma multiforme (GBM) (Press release, Telix Pharmaceuticals, SEP 20, 2022, View Source [SID1234619709]).

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The primary objective of the IPAX-1 study was to evaluate the safety and tolerability profile of intravenous 131I-IPA administered concurrently with second line EBRT in patients with recurrent GBM. Secondary objectives were to determine optimal dosing, biodistribution and radiation absorption into the tumour, as well as assess preliminary efficacy through clinical and imaging-based assessment of tumour response.

Final data up to the completion of the post-study follow-up period confirms the study has met its primary objective, demonstrating the safety and tolerability profile of TLX101 at the dosing range tested. The study also delivered encouraging preliminary efficacy data for further evaluation, demonstrating a median overall survival (OS) of 13 months from the initiation of treatment in the recurring setting, or 23 months from initial diagnosis. Given that GBM has a median survival from initial diagnosis of 12-15 months, the overall survival improvement trend seen in this patient population clearly warrants further evaluation in a larger patient population.

Recurrent GBM is a highly aggressive cancer that progresses rapidly, and for which there are few effective treatment options. TLX101 is a systemically administered targeted radiation therapy that targets L-type amino acid transporter 1 (LAT-1), which is typically over- expressed in GBM. TLX101 has been granted orphan drug designation in the United States and Europe.

IPAX-1 Results Summary

10 patients were enrolled of whom 9 received the full study treatment dosing of ~2GBq (2000 MBq) of TLX101, either in the form of a single administration or one of two triple-fractionated regimens. The results demonstrated all dosing regimens, in combination with EBRT, were well tolerated:

Dosimetric analysis demonstrates that radiation exposure to key organs is well within acceptable safety limits.
The most frequent treatment emergent adverse events (TEAEs) were decreased lymphocyte count, fatigue, headache and hiccups, which occurred in three patients (30%), followed by decreased platelet count, diarrhea, cerebral oedema (swelling), and insomnia, which occurred in two patients (20%).
Except for cerebral oedema (swelling), a typical side-effect of radiation to the brain, adverse events were of low grade, did not show any trends or patterns and were clinically manageable, with a significant proportion deemed unrelated to therapy. The therapy was generally well tolerated by patients.
Overall survival (OS) was a median of 13 months, from initiation of therapy in the recurrent disease setting.
Of the nine patients who received conventional imaging, four (44%) exhibited stable disease at day 135 and two (22%) at day 180, determined by longitudinal imaging.
Two patients remain alive at the time of study report.
Dr. Colin Hayward, Chief Medical Officer at Telix said, "We are pleased to report this final outcome, which will be submitted for publication. We can reconfirm that TLX101 has demonstrated safety and tolerability profile and encouraging early efficacy data. The median overall survival of 13 months from initial treatment in the recurrent second line setting reinforces the validity of further investigation and dose escalation of TLX101 in patients with GBM. Due to the aggressive nature of this cancer and limited treatment options, we are experiencing a high level of interest in the follow-on study that Telix is now undertaking in newly diagnosed patients, as a front-line therapy in combination with standard of care treatment. In parallel we will continue to study TLX101 in the recurrent setting."

Dr Josef Pichler, Kepler University Hospital, Austria and Principal Investigator in the IPAX-1 study said, "When you consider that GBM has a median survival from initial diagnosis of 12-15 months, the potential benefit demonstrated in relapsed patients, in a second-line setting is encouraging. We are very motivated to continue to investigate TLX101 in a larger patient population in the planned Phase II IPAX-L (Linz) study underway at Kepler University Hospital, with the goal of collecting additional safety and efficacy data for TLX101 in in combination with EBRT in patients with relapsed-glioblastoma."

On September 20, 2022 Therapeutic Solutions International (TSOI), a clinical stage regenerative medicine and immunotherapy company, reported it has entered into an agreement with GHS Investments, LLC ("GHS") to purchase up to $10,000,000 of Registered Common Stock (Press release, Therapeutics Solutions International, SEP 20, 2022, View Source [SID1234619708]).

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The agreement is on a look-back basis and there are no make-up provisions, a true non-toxic equity investment. GHS is a leading private investment and management group providing financial solutions for high potential small cap enterprises. GHS has made investments into multiple successful portfolio companies in the nano-market cap space that are seeking capital to measurably grow and scale their existing businesses to take advantage of emerging market sectors.

"This financing will allow the acceleration of our current Phase III clinical trial assessing efficacy of JadiCells, a novel adult stem cell, for treatment of COVID-19 associated lung injury," said Timothy Dixon, President, and CEO of Therapeutic Solutions International. "The implications of this trial are far-reaching in that success will open the door for entry into other pulmonary indications including ‘long COVID’ which remains a significant health problem."

Therapeutic Solutions International has 66 filed and issued patents, multiple IND’s covering Chronic Traumatic Encephalopathy (CTE), Acute Respiratory Distress Syndrome (ARDS), Chronic Obstructive Pulmonary Disease (COPD), and solid tumor Cancer’s as well as numerous preclinical and pilot clinical data around immunotherapy, oncology, and stem cell therapeutics.

On September 20, 2022 ExThera Medical reported that published data from a preliminary European study demonstrating in vitro adsorption of human circulating tumor cells (CTC) has been corroborated at a major US cancer center (Press release, ExThera Medical, SEP 20, 2022, View Source [SID1234619707]). CTCs are responsible for the often-fatal spread or metastasis of localized cancers to other parts of the body.

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This earlier German study confirmed that cultured neuroblastoma, prostate, and leukemia CTCs bind to the adsorption media in the company’s Seraph 100 Microbind Affinity Blood Filter (Seraph 100), which was developed to remove bacteria and viruses, often in immunocompromised patients. The recent USA study reconfirmed prostate CTC binding, and demonstrated binding of metastatic pancreatic, breast, lung and colon cancer CTCs isolated from the blood of patients who underwent conventional cancer therapies.

"These results await a peer-reviewed publication, but they are encouraging and warrant clinical study ASAP," said Robert Ward, CEO for ExThera Medical. "If clinical research confirms safety and efficacy, we see the possibility of a dialysis-like therapy that might prevent metastasis or extend the life of patients with existing metastatic cancer. Based on our experience treating COVID-19 and sepsis, we expect that even repeated and/or regular treatments with Seraph 100, would be well tolerated by patients, compared to chemo-radiation therapies." CTC levels in blood drawn from cancer patients can be monitored by existing diagnostic tests and help predict Overall Survival (OS) of cancer patients. However, no therapy is currently available to remove CTCs directly from the blood in quantities that could extend OS.

The European results were first presented in Sept 2021 at the Deutsche Gesellschaft für Nephrologie (DGfN) conference in Berlin as part of a scientific collaboration with University Hospital Frankfurt to evaluate clinical feasibility of metastatic cancer cell removal from the bloodstream: "Absorption of Circulating Tumor Cells by Hemoperfusion." (View Source). Other results also demonstrated reduction in cancer exosomes (CE’s).

"We are extremely excited by the results because these data suggest that Seraph 100 filter could make an impact on the outcomes of patients with metastatic cancer. We do not have effective treatments for many cancers after metastasis, and these data suggest that we can use a filter technology to perform ‘oncopheretic treatment,’ which could be a candidate therapy for the National Foundation for Cancer Research (NFCR) Cancer Moonshot program." said Lakhmir Chawla, MD and Medical Advisory Chair for ExThera Medical.

Based on these datasets, ExThera Medical plans to open a cancer hemadsorption Investigational Device Exemption (IDE) trial with the FDA by Q2, 2023.

Metastatic cancer research is a critical area of clinical research and represents a significant patient population. It is estimated that more than 600,000 patients in the United States will die from cancer in 20221, of which 90% will be from metastatic causes2. Metastatic cancer lacks effective therapies as it is often resistant to chemotherapy, radiation, and immunotherapy. Published studies show that the concentration of CTC’s and CEs in a patient’s blood is linked to outcomes in metastatic cancer. Higher counts of CTC and CE cells in the blood are linked to higher probability of death. Experimental methods which remove both CTCs and CEs have been shown to improve outcomes in animals. CTCs and CEs are key pathways for cancer progression and metastasis. Effective removal of CTCs and CEs is therefore likely to impact outcomes in patients with metastatic cancer.

Ward continued, "The observed rapid removal of CTCs and CEs from blood appears similar to the reduction rate we’ve seen for bacterial and viral pathogens when treating bloodstream infections with Seraph 100. We are committed to additional testing of this novel treatment to support the vision of a new therapy for late stage/metastatic cancer patients."

On September 20, 2022 Castle Biosciences, Inc. (Nasdaq: CSTL), a company improving health through innovative tests that guide patient care, reported that it will present the Company’s foundational guideposts – exceptional employees, continuous evolution and improvement, and customer and solution centric – as well as three-year financial targets (Press release, Castle Biosciences, SEP 20, 2022, View Source [SID1234619706]).

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"The guideposts presented today – exceptional employees, continuous evolution and improvement, and customer and solution centric – are firmly grounded in Castle’s mission, vision and values, and are foundational to how we operate our business," said Derek Maetzold, president and chief executive officer of Castle Biosciences. "We expect these principles to drive continued value creation and allow us to continue to meet the evolving needs of clinicians and their patients to improve shared decision-making."

"With Castle’s strong balance sheet, focused investments in our growth plans, and innovative portfolio of tests, we believe we are well-positioned to achieve our three-year financial targets, including anticipated total revenue of $255-$330 million for the year ending December 31, 2025," said Frank Stokes, chief financial officer of Castle Biosciences. "Additionally, we expect we will continue to see strong top-line growth and gross margins, balanced by disciplined capital allocation, which should contribute to our anticipated net operating cash flow positivity by 2025."

Maetzold and Stokes will be joined by the following Castle leaders and key opinion leader discussing the Company’s dermatology, gastroenterology and mental health tests, as well as its inflammatory skin disease pipeline program: Robert Cook, Ph.D., Castle Biosciences’ senior vice president, research and development; Matthew Goldberg, M.D., F.A.A.D., Castle Biosciences’ medical director; Craig Munroe, M.D., Castle Biosciences’ gastroenterology medical director; and Brent Moody, M.D., F.A.C.P., F.A.A.D., dermatologist and Mohs surgeon at Skin Cancer Surgery Center in Nashville, Tennessee.

Prepared remarks for Castle’s Investor Day will begin today at 4:00 p.m. Eastern time, followed by a Question & Answer session. During the webcast, Castle will present a slide deck associated with the event, which has been posted to the Investor Relations page of the Company’s website (View Source).

To register for the virtual event, please visit the Events & Presentations section of the Company’s investor relations page (View Source). A replay of the webcast will be available following the conclusion of the broadcast.

On September 20, 2022 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported an agreement with Takeda to license the worldwide research and development and commercial rights to alisertib, a selective, small-molecule, orally administered inhibitor of aurora kinase A (Press release, Puma Biotechnology, SEP 20, 2022, View Source [SID1234619705]). Alisertib is an adenosine triphosphate–competitive and reversible inhibitor of aurora kinase A and results in disruption of mitosis leading to apoptosis of rapidly proliferating tumor cells that are dependent on aurora kinase A. Alisertib has been tested in clinical trials in patients with metastatic cancers including breast cancer, small cell lung cancer, head and neck cancer, ovarian cancer, peripheral T cell lymphoma and acute myeloid leukemia.

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Under the terms of the agreement, Puma will assume sole responsibility for the global development and commercialization of alisertib. Takeda will receive an upfront license fee of $7 million and is eligible to receive potential future milestone payments of up to $287.3 million upon Puma’s achievement of certain regulatory and commercial milestones over the course of the agreement, as well as tiered royalty payments for any net sales of alisertib.

Puma initially intends to focus the development of alisertib on the treatment of patients with metastatic estrogen receptor-positive (ER-positive) HER2-negative breast cancer, triple-negative breast cancer and small cell lung cancer. In ER-positive HER2-negative breast cancer, alisertib has previously been tested in a Phase II clinical trial as a single agent (Lancet Oncology 2015), in a Phase II randomized clinical trial as a single agent compared to a combination with fulvestrant (SABCS 2020) and in a Phase II randomized clinical trial in combination with paclitaxel compared to paclitaxel monotherapy (JAMA Network Open 2021). In triple-negative breast cancer, alisertib has previously been tested in a Phase II clinical trial as a single agent (Lancet Oncology 2015) and in a randomized clinical trial in combination with paclitaxel compared to paclitaxel monotherapy (JAMA Network Open 2021). Alisertib has demonstrated meaningful clinical activity in these populations and most notably in ER-positive breast cancer patients who have been previously treated with a CDK4/6 inhibitor (JAMA Network Open 2021). Alisertib has also been previously tested in small cell lung cancer in a Phase II clinical trial as a single agent (Lancet Oncology 2015) and in a Phase II randomized clinical trial in combination with paclitaxel compared to paclitaxel monotherapy (Journal of Thoracic Oncology 2020).

"There continues to be a need for new drugs for the treatment of metastatic ER- positive, HER2-negative breast cancer and triple negative breast cancer," said Joyce A. O’Shaughnessy, M.D., the Celebrating Women Chair in Breast Cancer Research at Baylor University Medical Center, Texas Oncology, and Chair of Breast Cancer Research for the US Oncology Network in Dallas, Texas. "The results from the clinical trials of alisertib in these two indications are encouraging and suggest that the drug may be able to provide a clinical benefit to these patient populations, and, due to its novel mechanism, alisertib may be able to provide a benefit in patients who have developed resistance to other treatments modalities," said Dr. O’Shaughnessy.

"Treatment options for patients with small cell lung cancer that has progressed on or after platinum-based chemotherapy are limited, and there is an urgent need for new drugs to treat this patient population," said Taofeek K. Owonikoko, MD, PhD, Chief of the Division of Hematology/Oncology and Associate Director for Translational Research and Co-Leader of the Cancer Therapeutics Program at the UPMC Hillman Cancer Center. "The results from the clinical trials of alisertib in small cell lung cancer suggest that the drug may represent a potentially promising treatment option for these patients and more specifically for patients with molecularly defined tumors that are likely to respond to an aurora kinase A inhibitor such as alisertib," said Dr. Owonikoko.

Alan H. Auerbach, Chief Executive Officer, President and Founder of Puma stated, "We are pleased to be able to complete this licensing agreement with Takeda for alisertib. To date, alisertib has demonstrated strong evidence of antitumor activity, both as a single agent and in combination with other anticancer drugs, in patients with metastatic ER-positive and triple negative breast cancer, as well as in small cell lung cancer. We look forward to the continued development of alisertib."

Puma will host a conference call today at 2:00 p.m. PDT/5:00 p.m. EDT to discuss the alisertib licensing agreement. The call may be accessed by dialing (877) 709-8150 (domestic) or (201) 689-8354 (international). Please dial in at least 10 minutes in advance and inform the operator that you would like to join the "Puma Biotechnology Conference Call." A live webcast of the conference call and presentation slides may be accessed on the Investors section of the Puma Biotechnology website at View Source A replay of the call will be available shortly after completion of the call and will be archived on Puma’s website for 90 days.