On November 16, 2023 Curium, a world leader in nuclear medicine, reported that in partnership with its exclusive distributor SYN Innovation Laboratories in Greece, the first patients in Greece have been injected with PYLCLARI (INN: Piflufolastat (18F) also known as (18 F)-DCFPyL, indicated for the detection of prostate-specific membrane antigen (PSMA) positive lesions with positron emission tomography (PET) in patients with prostate cancer in the following clinical settings (Press release, Curium, NOV 16, 2023, View Source [SID1234637734]):

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Primary staging of patients with high-risk PCa prior to initial curative therapy
To localize recurrence of PCa in patients with a suspected recurrence based on increasing serum prostate-specific antigen (PSA) levels after primary treatment with curative intent
Benoit Woessmer, PET Europe CEO at Curium commented, "We are thrilled that patients in Europe are finally able to benefit from PYLCLARI, and in particular those patients in Greece via our strong partnership with SYN Innovation Laboratories. As a world leader in nuclear medicine, Curium is pleased to be improving the choice of diagnostic tools available to physicians in Greece to diagnose prostate cancer – ultimately for the benefit of prostate cancer patients."

Savvas Thalasselis, Managing Director, SYN Innovation Laboratories SA commented: "Today’s announcement of the first dose of PYLCLARI in Greece is an important milestone for the detection of prostate cancer, in particular for the primary staging of patients with high-risk prostate cancer prior to initial curative therapy. Our long-term partnership with Curium has demonstrated our commitment to diagnosing patients with cancer, and we look forward to further supporting Curium with their future pipeline of diagnostic and therapeutic products."

Today’s announcement follows the decision in July 2023 by the European Commission granting marketing authorization for PYLCLARI in the European Union. SYN Innovation Laboratories has been a partner with Curium since 2017, with exclusive manufacturing and distribution rights for Curium’s wide range of positron emission tomography products in Greece. SYN Innovation Laboratories will manufacture PYLCLARI at its facilities in Athens, Greece.

On November 16, 2023 Circio Holding ASA (OSE: CRNA), a biotechnology company developing novel circular RNA and immunotherapy medicines, reported that it has entered into a collaboration with Georgetown University as part of a collaborative research support agreement with Janssen Scientific Affairs, LLC (Janssen) and a drug supply agreement with Bristol Myers Squibb (BMS) to test its drug candidate TG01 in combination with daratumumab (anti-CD38) and nivolumab (anti-PD1) in patients with RAS-mutated pancreatic cancer and patients with non-small cell lung cancer (NSCLC) (Press release, Circio, NOV 16, 2023, View Source [SID1234637733]).

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Mutations in the RAS-family of genes are a major cause of cancer and found in over 90% of pancreatic and 30% of NSCLC cancer patients. RAS-mutated cancers typically have poor prognosis, and few targeted treatment options exist. The only approved RAS-targeting pharmaceuticals are small molecule inhibitors of the specific G12C KRAS mutation, which covers around 40% of RAS-mutated lung cancers, and the medical need for novel treatment alternatives for mutant RAS cancer remains high. Furthermore, anti-PD1 resistance is emerging as a major problem in immunotherapy, and more than 80% of patients with advanced tumors still do not respond to such treatment.

To further study this unmet medical need, Georgetown University is pursuing a phase 2 study to test the combination of daratumumab provided by Janssen, nivolumab provided by BMS, and TG01 provided by Circio in immunotherapy-naïve pancreatic cancer and in anti-PD1 resistant NSCLC. The scientific hypothesis behind the study is based on ground-breaking research led and published by Prof. Samir Khleif and colleagues, demonstrating that elimination of dysfunctional CD8 T-cells by anti-CD38, followed by priming of new effector T-cells by a cancer vaccine, reinstated and strengthened efficacy of PD1 checkpoint blockade in pre-clinical models.

Prof. Samir Khleif, Georgetown University, said: "Resistance to checkpoint blockade remains one of the most challenging problems in treating cancer patients and represents a significant unmet medical need. We are very pleased to have established this collaboration to test a novel immunotherapy combination regimen with the intention of overcoming immunotherapy resistance. The combination of anti-CD38, anti-PD1 and a cancer vaccine has demonstrated highly potent in preclinical in vivo models, and we are eager to evaluate how these findings will translate in the clinic."

The trial will be led by Georgetown University in Washington D.C, USA. The triple therapy combination will be tested in 54 patients in total, 27 immunotherapy-naïve KRAS-mutated patients with pancreatic cancer and 27 KRAS-mutated patients with NSCLC who have progressed on prior anti-PD1 therapy.

Dr. Erik Digman Wiklund, Chief Executive Officer of Circio Holding ASA, added: "We continue to see increasing interest in our mutant KRAS program, and the Georgetown phase 2 study will be the third investigator-sponsored clinical trial with the enhanced TG01 vaccine. This will be the first time TG01 is tested in lung and non-resectable pancreatic cancer, potentially opening up new indications for future development. Collaborations such as this is at the core of the TG01 development strategy, and shows that we are continuing to execute on our strategy of advancing our KRAS program through external development in multiple settings and geographies."

Circio has been awarded two prestigious research grants from Innovation Norway (IN) and the Norwegian Research Council (NRC) to advance the TG program in several clinical studies. This phase 2 trial at Georgetown will be the first study where TG01 is combined with anti-CD38 and anti-PD1, and the first time the vaccine is tested in NSCLC. Circio will be responsible for TG01 drug supply and scientific support towards specific KRAS-related immunological assays, supported through the IN and NRC research grants. Janssen will contribute with funding for the study and daratumumab supply, and BMS will provide supply of nivolumab. The study protocol has been approved by the US FDA, and it is anticipated that the first patient will be enrolled at Georgetown before the end of 2023.

On November 16, 2023 University of Tsukuba (President: Kyosuke Nagata) and Astellas Pharma Inc. (TSE: 4503, President and CEO: Naoki Okamura, "Astellas") reported that they have signed a letter of confirmation regarding a strategic partnership to accelerate the digitalization of the drug discovery research field, as well as the development of the life science ecosystem in Tsukuba and Kashiwa-no-ha, and to further accelerate innovative drug discovery research and development (Press release, Astellas, NOV 16, 2023, View Source [SID1234637732]).

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Under this agreement, the two parties will exchange information on and discuss:
Promotion of drug discovery and other research, and creation of new startups through industry-academia collaboration between the two parties
Utilization of cutting-edge research equipment, drug discovery-related data and research seeds mutually owned by the two parties
Implementation of discussions and seminars to accelerate and develop collaborative research already conducted by the two parties
Promotion of drug discovery research and creation of new startups through exchange and communication with third-party venture company innovators in residence at SakuLabTM-Tsukuba*1
Based on this agreement, the University of Tsukuba will establish an office in Astellas’ SakuLabTM-Tsukuba for the Tsukuba Digital-Bio International Center*2, where they are participating as a lead organization. The center will provide an environment where researchers from different fields including researchers specializing in medicine, biotechnology, and the AI/digital analytics field from the University of Tsukuba and Astellas’ researchers specializing in drug discovery can discuss freely and energetically, aiming to create a place for innovative and active co-creative research through the fusion of different fields.

Hiroyuki Nishiyama, M.D., Ph.D., Leader of Tsukuba Digital-Bio International Center
"In western drug discovery ecosystems, researchers and innovators have quick and easy access to cutting-edge research results and trends in their fields of expertise. Japanese pharmaceutical companies tend to look there because they can’t obtain enough information in Japanese drug discovery ecosystems. Against this background, we have been discussing with Astellas for the past one and a half years to change the conventional frame of reference. I believe that we can flexibly and speedily formulate new joint research themes not limited to specific fields and execute efficient research by sharing our research information (seeds) and areas of research interest at Astellas. We will work to build a drug discovery ecosystem in Japan that will enable start-ups to be implemented in society. We hope that this initiative will be one opportunity to overcome the barrier known as the "valley of death" that exists when translating academia research results into social implementations."

Yoshitsugu Shitaka, Ph.D., Chief Scientific Officer (CScO) of Astellas
"We are very pleased to confirm this strategic partnership with the University of Tsukuba, the flagship university of Tsukuba Science City. We believe our scope of knowledge and experience in drug research, and our global network will pair well with the University of Tsukuba’s outstanding expertise in medicine, biotechnology, and the AI/digital field. Together we aim for further growth in the life science ecosystem in Tsukuba and the Kashiwa-no-ha areas, with SakuLabTM-Tsukuba as a starting point for innovation. We envision the collaboration will enable visionary ideas and specialized knowledge to converge, turbocharging the development of pioneering healthcare solutions."

Astellas has already reflected the impact from this agreement in its financial forecast of the current fiscal year ending March 31, 2024.

On November 16, 2023 Alpha Tau Medical Ltd. ("Alpha Tau", or the "Company") (NASDAQ: DRTS, DRTSW), the developer of the innovative alpha-radiation cancer therapy Alpha DaRT, reported third quarter 2023 financial results and provided a corporate update (Press release, Alpha Tau Medical, NOV 16, 2023, View Source [SID1234637731]).

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"This year has already seen tremendous progress, as we advance our ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma, which is expected to produce data in 2024, and continue to initiate a series of feasibility trials in difficult-to-treat internal organ tumors with high unmet need, such as pancreatic and liver cancers," stated Alpha Tau CEO Uzi Sofer. "We are looking forward to meaningful inflection points during the rest of 2023, including interim safety and feasibility data from our pancreatic cancer trial in Montreal, and our forthcoming submission in Japan for pre-market approval. In parallel, we are preparing for future product launches by advancing our commercial planning activities and solidifying our supply chain, which was recently bolstered by a valuable land grant in Jerusalem that is expected to increase our future manufacturing capacity as well as the leasing of a second manufacturing site in the U.S. Alpha Tau remains adequately capitalized to support all of these programs over the coming years," he concluded.

Recent Corporate Highlights:

● In October, the Company announced that it had entered into a long-term lease agreement for a standalone building of over 14,000 rentable square feet in Hudson, NH, with the intention of erecting the Company’s second U.S. manufacturing site, alongside its first site in nearby Lawrence, MA.

● In October, the Company announced that Dr. Stephen Hahn, a former commissioner of the U.S. Food and Drug Administration (FDA) and a distinguished expert in the field of radiation oncology and translational clinical research, has joined its Scientific Advisory Board.

● In September, the first patient with advanced inoperable pancreatic cancer was treated with Alpha DaRT at Hadassah Medical in Jerusalem, Israel, in parallel to the Company’s ongoing safety and feasibility trial for the treatment of advanced inoperable pancreatic cancer currently underway in Montreal, Canada.

● In August, Alpha Tau reported long-term safety and tumor control outcomes data for patients with unresectable, recurrent, or locally advanced head and neck or skin tumors treated with Alpha DaRT across four prospective trials conducted at several international institutions. In this analysis, 81 lesions were treated in 71 patients. The median follow-up was 14 months (range: 2-51 months). A complete response (CR) was observed in 89% of treated lesions (n=72), 10% (n=8) demonstrated a partial response, and one patient was not evaluable. The two-year actuarial local recurrence-free survival (LRFS) rate was 77% [95% CI: 63–87%]. Twenty percent of patients developed treatment-related acute grade 2 toxicity (such as dermatitis radiation, local pain at the treatment site or pruritus), which subsequently resolved with conservative treatment; there were no grade 3 or higher related acute toxicities reported. There were no grade 2 or higher ‘late toxicities’, defined as toxicities occurring six months after Alpha DaRT treatment or later, observed in this cohort.

Upcoming Near-Term Milestones

● Expecting to release interim safety and feasibility data in Q4 2023 from the first five patients treated in the Company’s study examining the use of Alpha DaRT to treat patients in Montreal, Canada with advanced inoperable pancreatic cancer. For more information please see here: View Source

● Expecting to submit to the PMDA in Japan in Q4 2023 for pre-market approval for Alpha DaRT in patients with recurrent head & neck cancer.

● Planning treatment of the first patient in the Canadian liver metastases safety and feasibility trial in Q4 2023 or Q1 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Planning treatment of the first patient in the Israeli recurrent lung cancer safety and feasibility trial in H1 2024. The trial is currently open for recruitment; for more information please see here: View Source

● Targeting first brain cancer treatment in H1 2024.

● Targeting completion of patient recruitment in the ReSTART pivotal U.S. multi-center trial in recurrent cutaneous squamous cell carcinoma in Q2 2024. For more information please see here: View Source

Financial results for nine months ended September 30, 2023

R&D expenses for the nine months ended September 30, 2023 were $18.9 million, compared to $15.5 million for the same period in 2022, due to increased employee compensation and benefits, including share-based compensation, increased pre-clinical study and clinical trial expenses particularly in our U.S. multi-center pivotal trial, and reduced government grants, offset by lower expenses in Japan because of the completion of our clinical study in Japan last year.

Marketing expenses for the nine months ended September 30, 2023 were $1.5 million, compared to $0.6 million for the same period in 2022, due to increased employee compensation and benefits, including share-based compensation for marketing personnel including our chief commercial officer hired in 2022, as well as increased marketing activities.

G&A expenses for the nine months ended September 30, 2023 were $5.3 million, compared to $8.1 million for the same period in 2022, due to decreased compensation expenses as well as one-time expenses in 2022 associated with the Company’s merger with Healthcare Capital Corp.

Financial income, net, for the nine months ended September 30, 2023 was $4.0 million, compared to financial expense, net of $6.2 million, for the same period in 2022, due to a decrease in remeasurement of warrants, an increase in interest from bank deposits, and changes in foreign exchange rates.

For the nine months ended September 30, 2023, the Company had a net loss of $21.8 million, or $0.31 per share, compared to a net loss of $30.4 million, or $0.49 per share, in the same period of 2022.

Balance Sheet Highlights

As of September 30, 2023, the Company had cash, restricted cash, deposits and restricted deposits in the amount of $90.1 million, compared to $105.4 million on December 31, 2022. The Company expects that this cash balance will be sufficient to fund operations for at least two years.

On November 16, 2023 Alentis Therapeutics ("Alentis"), a clinical-stage biotechnology company developing treatments for Claudin-1 positive (CLDN1+) tumors and organ fibrosis, reported that the first patient has been dosed in a Phase 1/2 clinical trial of ALE.C04, a Claudin-1 (CLDN1) targeting investigational antibody for the treatment of CLDN1+ tumors (Press release, Alentis Therapeutics, NOV 16, 2023, View Source [SID1234637725]). The patient is enrolled under the Phase I program, led by Anthony El-Khoueiry, MD, Associate Director of Clinical Research, at University of Southern California (USC) Norris Comprehensive Cancer Center, part of Keck Medicine of USC.

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The open-label, multi-center, Phase 1/2 clinical trial (NCT06054477) will investigate ALE.C04 as a single agent and in combination with pembrolizumab (anti-PD-1 antibody) in 220 adults with recurrent or metastatic (R/M) head and neck squamous cell carcinoma. Endpoints include safety, tolerability, pharmacokinetics and anti-tumor efficacy.

"ALE.C04 is a first-in-class antibody for treating cancer and has shown much potential in preclinical models," said Luigi Manenti, MD, Chief Medical Officer of Alentis. "ALE.C04 is designed to kill CLDN1+ tumor cells directly and to break the check-point inhibitor treatment resistance by restoring immune cell trafficking."

Jacob Thomas, MD, principal investigator on the trial at USC Norris and Assistant Professor of Medicine at Keck School of Medicine of USC added, "Patients with R/M HNSCC have poor outcomes, and novel effective therapies are needed in this setting. The mechanism of action and preclinical data for ALE.C04 provide sound scientific rationale for its evaluation in HNSCC."

Prof. Josep Tabernero, Head of Medical Oncology at Vall d’Hebron University Hospital said, "This first-in-human trial will provide valuable information on ALE.C04 as a monotherapy and in combination with anti-PD-1 treatment. I am looking forward to the data and to developing ALE.C04 for other CLDN1+ tumors including colorectal cancer."

About ALE.C04
ALE.C04 is a first-in-class monoclonal antibody developed to specifically target exposed CLDN1 on cancer cells. This investigational antibody is designed to treat cancer in two ways: remodeling of the extracellular matrix, leading to improved NK and T-cell trafficking and direct tumor cell killing through the effector function. This unique mechanism of action provides ALE.C04 with therapeutic potential as a monotherapy and in combination. ALE.C04 received Fast Track designation from the Food and Drug Administration for the treatment of CLDN1+ HNSCC.

About HNSCC
Head and neck squamous cell carcinoma, or HNSCC, is the 6th most common cancer worldwide and because the number of cases is quickly rising, safer and more effective treatments are urgently needed. Despite advances in treatment, the 5-year survival rate remains at about 57%.