On June 11, 2024 TRACON Pharmaceuticals (NASDAQ: TCON), a clinical stage biopharmaceutical company utilizing a cost-efficient, CRO-independent Product Development Platform (PDP) to advance its pipeline of novel targeted cancer therapeutics and to partner with other life science companies, reported the publication of Phase 2 clinical data of its DNA damage repair inhibitor drug candidate, TRC102, in patients with glioblastoma in Clinical Cancer Research (Press release, Tracon Pharmaceuticals, JUN 11, 2024, View Source [SID1234644262]). The article, entitled, "Evaluating the Base Excision Repair Inhibitor TRC102 and Temozolomide for patients with Recurrent Glioblastoma in the Phase 2 Adult Brain Tumor Consortium Trial BERT," highlights the activity of TRC102 given in combination with Temodar chemotherapy in patients with recurrent glioblastoma: View Source

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TRC102 was evaluated in a Phase 2 trial in combination with Temodar in 19 patients with progressive or recurrent glioblastoma following surgical resection, Temodar and external beam radiotherapy. Extended survival was observed in two patients (progression-free survival ≥ 17 months and overall survival > 32 months), both of whom demonstrated significantly enriched signatures of DNA damage response (DDR), chromosomal instability, and cellular proliferation by RNA sequencing prior to initiating treatment with Temodar and TRC102. The study was completed by the Adult Brain Tumor Consortium and led by Manmeet Alhuwalia, MD while he was Chair of Neuro-Oncology at Cleveland Clinic prior to his appointment as Chief of Medical Oncology, Chief Scientific Officer, and Deputy Director of the Miami Cancer Institute. The authors concluded the study findings confirm the safety and feasibility of TRC102 given with Temodar for recurrent glioblastoma patients and warrant further evaluation of combination therapy in biomarker-enriched trials enrolling glioblastoma patients with baseline hyperactivated DDR pathways.

"We believe that the data generated to date provides a strong rationale for studying TRC102 in combination with Temodar and radiotherapy in newly diagnosed patients with malignant glioma," said James Freddo, M.D., Chief Medical Officer of TRACON. "The Clinical Cancer Research publication supports prior data published in Cancer Cell (View Source) that patients whose cancers demonstrate activation of DDR pathways may be particularly sensitive to the pharmacologic effects of TRC102."

Based on a 100% response rate (including a 20% complete response rate) in a Phase 1 clinical trial combining TRC102 with pemetrexed, cisplatin and radiation therapy in 15 patients with stage III non-squamous non-small cell lung cancer (View Source), TRC102 is currently being studied in a randomized Phase 2 clinical trial in combination with chemotherapy (pemetrexed, cisplatin or carboplatin) and radiation therapy for stage III non-squamous non-small cell lung cancer (NCT05198830: View Source;rank=6). This trial is sponsored by the National Cancer Institute (NCI) through a Cooperative Research and Development Agreement (CRADA). Determination of the primary endpoint of progression free survival is expected in 2025. TRACON and the NCI have a longstanding history of partnership to develop TRC102, whereby the NCI has funded six Phase 1 or Phase 2 trials through the CRADA.

About TRC102

TRC102 (methoxyamine) is a novel, clinical-stage small molecule inhibitor of the DNA base excision repair pathway, which is a pathway that causes resistance to alkylating and antimetabolite chemotherapeutics. TRC102 is currently being studied in multiple randomized Phase 2 clinical trial entitled Testing the Addition of an Anti-Cancer Drug, TRC102, to the Usual Chemotherapy Treatment (Pemetrexed, Cisplatin or Carboplatin) During Radiation Therapy for Stage III Non-Squamous Non-Small Cell Lung Cancer (NCT05198830) that is sponsored by the NCI through a CRADA. TRC102 was granted orphan drug designation by the US FDA for the treatment of malignant glioma in 2020. For more information about the clinical trials, please visit TRACON’s website at www.traconpharma.com/clinical-trials.

About Malignant Glioma and Glioblastoma
Glioblastoma (GBM) is a rapidly growing malignant glioma that develops from glial cells (astrocytes and oligodendrocytes) that support the health of the nerve cells within the brain. GBM is the most invasive type of glial tumors, rapidly growing and commonly invading into nearby brain tissue. The National Cancer Institute estimates that approximately 22,850 adults are diagnosed with brain and other nervous system cancers annually in the U.S. and approximately 15,320 of these diagnoses will result in death. GBM has an incidence of two to three per 100,000 adults per year in the U.S., and accounts for 52 percent of all primary brain tumors.

On June 11th, 2024 – Orphelia Pharma, a pharmaceutical company dedicated to the development and marketing of pediatric and orphan medicines, reported that KIZFIZO, temozolomide oral suspension, will be included in the MetroWILMS-1906 study (EudraCT: 2021-002540-67, NCT05384821) (Press release, ORPHELIA Pharma, JUN 11, 2024, View Source;utm_medium=rss&utm_campaign=orphelia-pharma-to-collaborate-with-oscar-lambret-clinical-center-to-study-kizfizo-the-first-pediatric-drinkable-formulation-of-temozolomide-for-the-treatment-of-refractory-or-relapsed-nephrob [SID1234644263]). MetroWILMS is a French, multicentric, non-randomized, Phase 1-2 clinical trial to study the efficacy and safety of metronomic chemotherapy, including temozolomide, for the treatment of refractory or relapsed nephroblastoma (Wilms tumor). MetroWILMS is sponsored by the Oscar Lambret clinical center on behalf of the Société Française des Cancers de l’Enfant (SFCE), Nephroblastoma committee.

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Pediatric renal (kidney) tumors account for 4%-11% of all childhood cancers, the most common of which being nephroblastoma or Wilms tumor. It affects young children, most of the cases being diagnosed before 5 years of age. Despite a good prognosis, 10 to 15 % of patients present a refractory Wilms tumor or experience relapse and bear a dismal prognosis.

As part of the MetroWILMS protocol, KIZFIZO (under the name KIMOZO currently in use in France) will be administered for the treatment of refractory/relapsed Wilms tumors (after 1 or 2 lines of treatment or after 1 line for high risk relapse for which there would not be any curative therapy), using a metronomic schedule and in combination with other drugs (vincristine, irinotecan, etoposide and cis retinoic acid). MetroWILMS will include 28 pediatric patients, with a recruitment planned until October 2028.

"There is a major clinical need for an oral liquid form of temozolomide in various pediatric oncology indications, including in refractory or relapsed Wilms tumor", said Hélène Sudour-Bonnange, onco-pediatrician at Oscar-Lambret clinical center and principal investigator of MetroWILMS trial. "We believe that KIZFIZO oral suspension is especially well suited to treat our young patients."

"Refractory or relapsed nephroblastoma is a very rare indication, but this is well in line with Orphelia’s missions to help pediatric patients with rare cancers", said Jérémy Bastid, chief medical officer at Orphelia Pharma. "Should MetroWilms demonstrate a clinical benefit, we could consider expanding the label of KIFZIZO in this indication".

About KIZFIZO 40 mg/ml

KIZFIZO (temozolomide oral suspension, 40 mg/ml) is a ready-to-use oral liquid pediatric formulation of temozolomide developed for use in the treatment of relapsed or refractory high-risk neuroblastoma, which carry a very poor prognosis. This age-adapted and taste-masked formulation delivers an accurate dose in a small volume, while avoiding drug handling and caregiver exposure to temozolomide. It is the result of a collaboration between the pharmacists and clinicians at Gustave Roussy hospital and the development team at Orphelia Pharma.

In March 2022, KIZFIZO (under the trade name KIMOZO) was granted Early Access Authorization (Autorisation d’Accès Précoce) by the French authorities, for the treatment of refractory and relapsed high-risk neuroblastoma as monotherapy or in combination with irinotecan or topotecan.

KIZFIZO has received an Orphan Drug Designation from the EMA and the FDA and the formulation is covered by granted patents in Europe and the US. The company filed an MAA with the EMA in the summer of 2023.

On June 10, 2024 Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) reported that the European Commission has approved a Chugai originated anaplastic lymphoma kinase (ALK) inhibitor Alecensa (generic name : alectinib) monotherapy, as adjuvant treatment following tumour resection for adult patients with ALK-positive non-small cell lung cancer (NSCLC) at high risk of recurrence (Stage IB [tumors ≥ 4 cm]–IIIA NSCLC [7ᵗʰ edition UICC/AJCC]) (Press release, Chugai, JUN 10, 2024, View Source [SID1234644221]). Data from the Phase III ALINA trial, where Alecensa demonstrated a 76% reduction in the risk of disease recurrence or death in people with resected ALK-positive NSCLC, supported the marketing authorisation application.1

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"We are very pleased that Alecensa, a Chugai originated medicine, received approval in Europe following the U.S. approval for adjuvant treatment of ALK-positive early-stage NSCLC. We believe that this approval will have a significant impact, providing a new treatment opportunity for patients who have dealt with the risk of recurrence even after undergoing tumor resection. We remain committed to working with Roche to bring the benefits of this drug to patients around the world." said Chugai’s President and CEO, Dr. Osamu Okuda.

In the ALINA study, Alecensa reduced the risk of disease recurrence or death by 76% (hazard ratio [HR]=0.24, 95% CI: 0.13-0.43, p<0.0001) compared with platinum-based chemotherapy in people with completely resected IB (tumors ≥ 4 cm) to IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC.1 In an exploratory analysis, an improvement of central nervous system disease-free survival was observed (HR=0.22; 95% CI: 0.08-0.58) compared with platinum-based chemotherapy.1 This is of particular importance for people with ALK-positive NSCLC, who are at greater risk of developing brain metastases than those with other types of NSCLC.2 The safety and tolerability of Alecensa in the ALINA trial were generally consistent with previous trials in the metastatic setting and no unexpected safety findings were observed.1 These data were published in the New England Journal of Medicine in April 2024.

Alecensa is the preferred treatment option for patients with advanced ALK-positive NSCLC. Approved in more than 100 countries as a first- and second-line treatment, more than 94,000 patients with advanced disease have been treated with Alecensa in clinical practice. Following its approval in the adjuvant treatment setting, Alecensa could play a pivotal role in ALK-positive resectable disease, where there is a significant unmet medical need. Today’s approval in Europe follows the April 2024 U.S. Food and Drug Administration (FDA) approval of Alecensa as adjuvant treatment following tumor resection for patients with ALK-positive NSCLC (tumors ≥ 4 cm or node positive), as detected by an FDA-approved test. Submissions to additional health authorities worldwide are ongoing to bring this new treatment option to as many patients as possible.

To support clinicians’ decision-making, testing of resected surgical tissue or biopsy for ALK, EGFR and PD-L1 biomarkers in patients with stage IB to IIIA and selected IIIB (UICC/AJCC 8th edition) NSCLC, in addition to in the advanced setting, is recommended by international guidelines, including the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology (NCCN Guidelines).

About the ALINA study
The ALINA study [NCT03456076] is a Phase III, randomized, active-controlled, multicenter, open-label study evaluating the efficacy and safety of adjuvant Alecensa (alectinib) compared with platinum-based chemotherapy in people with resected Stage IB (tumors ≥ 4 cm) to IIIA (UICC/AJCC 7th edition) anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). The study included 257 patients who were randomly assigned to either the Alecensa or chemotherapy treatment arm. The primary endpoint is disease-free survival. Secondary outcome measures include overall survival and percentage of patients with adverse events.

About Alecensa
Alecensa is a highly selective, central nervous system-active, oral medicine created at Chugai, a member of the Roche Group, for people with NSCLC whose tumors are identified as ALK-positive. Alecensa is already approved in over 100 countries as an initial (first-line) and second-line treatment for ALK-positive, metastatic NSCLC, including in the United States, Europe, Japan and China. Alecensa was approved by the U.S. Food and Drug Administration (FDA) in April 2024 as adjuvant treatment following tumor resection for patients with ALK-positive NSCLC (tumors ≥ 4 cm or node positive), as detected by an FDA-approved test, and in June 2024 by the European Commission, as a monotherapy for adjuvant treatment following tumor resection for adult patients with ALK-positive NSCLC at high risk of recurrence (Stage IB [tumors ≥ 4 cm]–IIIA NSCLC [7ᵗʰ edition UICC/AJCC]). In Japan, Alecensa has also been approved for the treatment of recurrent or refractory ALK fusion gene-positive anaplastic large cell lymphoma.

About lung cancer
Lung cancer is one of the leading causes of cancer death globally.3 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day.3 In Japan, 127 thousand people are affected by this disease (2019).4 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and small-cell lung cancer. NSCLC is the most prevalent type, accounting for around 85% of all cases.5 Today, about half of all people with early lung cancer (45-76%, depending on disease stage) still experience a cancer recurrence following surgery, despite adjuvant chemotherapy.6 Treating lung cancer early, before it has spread, may help prevent the disease from returning and provide people with the best opportunity for a cure.7

Trademarks used or mentioned in this release are protected by law.

On June 10, 2024 Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer, reported the completion of patient enrollment for STAR-221, a Phase 3 study in collaboration with Gilead Sciences, evaluating the combination of the Fc-silent anti-TIGIT antibody domvanalimab plus the anti-PD-1 monoclonal antibody zimberelimab and chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction or esophageal adenocarcinoma (Press release, Arcus Biosciences, JUN 10, 2024, View Source [SID1234644237]).

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"STAR-221 completed enrollment well ahead of schedule, driven by significant interest from the global medical community in the potential for an anti-TIGIT-based regimen to address the high unmet need in this setting," said Dimitry S.A. Nuyten, M.D., Ph.D., chief medical officer of Arcus Biosciences. "Domvanalimab is the first and only anti-TIGIT antibody to be studied in a Phase 3 trial in upper gastrointestinal adenocarcinoma. We are now preparing for the readout and look forward to the potential opportunity to make a meaningful difference for patients with this disease."

Earlier this month at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, Arcus and Gilead presented results from Arm A1 of the Phase 2 EDGE-Gastric study evaluating the same regimen in the same setting as the STAR-221 Phase 3 study. Data from this arm of EDGE-Gastric showed that patients treated with domvanalimab plus zimberelimab and chemotherapy had a median progression-free survival (PFS) of 12.9 months, which exceeds the historical benchmarks for anti-PD-1 plus chemotherapy alone. Notably, nearly 60% of patients in the EDGE-Gastric study achieved PFS at 12 months, and the domvanalimab plus zimberelimab and chemotherapy regimen demonstrated sustained improvement across efficacy measures, including in those patients who have low PD-L1 expression. No unexpected safety signals were observed at the time of data cutoff, March 12, 2024. The domvanalimab plus zimberelimab and chemotherapy regimen was generally well tolerated and showed an overall safety profile consistent with the known safety profiles of each individual molecule to date.

Domvanalimab and zimberelimab are investigational molecules. Neither Gilead nor Arcus has received approval from any regulatory authority for any use of these molecules, and their safety and efficacy for the treatment of gastrointestinal cancers have not been established.

About the STAR-221 Study

The ongoing, global STAR-221 trial (NCT05568095) enrolled approximately 1,050 participants with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The primary endpoints of the study are overall survival in PD-L1-high tumors and in the intent-to-treat population (all PD-L1 levels); secondary endpoints include progression-free survival, objective response rate and duration of response. Participants were randomized 1:1 between two arms:

1600 mg of domvanalimab intravenously (IV) every four weeks plus 480 mg of zimberelimab IV every four weeks plus FOLFOX (oxaliplatin, leucovorin, fluorouracil) every two weeks or 1200 mg of domvanalimab plus 360 mg of zimberelimab every three weeks plus CAPOX (capecitabine and oxaliplatin) every three weeks
240 mg of nivolumab IV every two weeks plus FOLFOX every two weeks or 360 mg of nivolumab plus CAPOX every three weeks
About Domvanalimab

Domvanalimab is the first and most clinically advanced Fc-silent investigational monoclonal antibody that is specifically designed with Fc-silent properties to block and bind to the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), a checkpoint receptor on immune cells that acts as a brake on the anticancer immune response. By binding to TIGIT with Fc-silent properties, domvanalimab is believed to work by freeing up immune-activating pathways and activate immune cells to attack and kill cancer cells without depleting the peripheral regulatory T cells important in avoiding immune-related toxicity.

Combined inhibition of both TIGIT and programmed cell death protein-1 (PD-1) is believed to significantly enhance immune cell activation, as these checkpoint receptors play distinct, complementary roles in anti-tumor activity. Domvanalimab is being evaluated in combination with anti-PD-1 monoclonal antibodies, including zimberelimab, as well as other investigational cancer immunotherapies and A2a/A2b adenosine receptor antagonist etrumadenant, in multiple ongoing and planned early and late-stage clinical studies in various tumor types.

About Zimberelimab

Zimberelimab is an anti-programmed cell death protein-1 (PD-1) monoclonal antibody that binds PD-1, with the goal of restoring the antitumor activity of T cells. Zimberelimab has demonstrated high affinity, selectivity and potency in various tumor types.

Zimberelimab is being evaluated in the U.S. and globally as a foundational anti-PD-1 treatment option in multiple ongoing and planned early and late-stage clinical studies in combination with other immunotherapies, including investigational Fc-silent anti-TIGIT monoclonal antibody domvanalimab and A2a/A2b adenosine receptor antagonist etrumadenant.

Guangzhou Gloria Biosciences Co. Ltd., which holds commercialization rights for zimberelimab in greater China, has obtained approval for zimberelimab for the treatment of recurrent or metastatic cervical cancer and for relapsed or refractory classical Hodgkin’s lymphoma. Zimberelimab is not approved for any use in the U.S. or other regions outside of China. Gloria conducts its development and commercialization activities independent of Arcus and Gilead.

On June 10, 2024 InDex Pharmaceuticals Holding AB (publ) (under name change to Flerie AB) ("InDex Pharmaceuticals" or the "Company") reported that the reverse merger with Flerie Invest AB ("Flerie"), pursuant to the agreement entered into and announced on May 20, 2024, has been completed (Press release, InDex Pharmaceuticals, JUN 10, 2024, View Source [SID1234644222]). As a result thereof, the Company changes its name to Flerie AB and a new board and management take office.

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Completion of the reverse merger
On May 20, 2024 InDex Pharmaceuticals entered into a conditional agreement, to acquire all shares in Flerie (the "Transaction"). The Transaction constitutes a so-called reverse merger whereby Flerie becomes a wholly-owned subsidiary of InDex Pharmaceuticals.

The completion of the Transaction was, among other things, conditional upon resolutions at extraordinary general meetings of the Company. The extraordinary general meetings, held on June 10, 2024, resolved to adopt all of the board’s proposed resolutions related to the Transaction. The resolutions are further described in the bulletin from the meetings that was announced by the Company earlier today. In addition to the resolutions at the extraordinary general meetings, the Company and Flerie agree that all other conditions of the Transaction have been fulfilled. The Transaction has therefore today been completed.

The purchase price in the Transaction has been paid through an issue in kind of 6,073,952,948 new shares in the Company (the "Consideration Shares"). The Consideration Shares have been subscribed for by the former shareholders of Flerie in exchange for all shares in Flerie. Following registration of the Consideration Shares, the former shareholders of Flerie will initially hold approximately 91.9 per cent of the total number of shares and votes in the Company, prior to completion of the capital raise outlined in the company description published by the Company on May 27, 2024.

At the extraordinary general meetings held today June 10, 2024, it was, among other things, resolved to change the company name of the Company to Flerie AB and to appoint Thomas Eldered, Cecilia Edström, Anders Ekblom and Jenni Nordborg as new board members of the Company, with Thomas Eldered as chairman. Flerie’s CEO Ted Fjällman has been appointed CEO of the Company and Flerie’s CFO and deputy CEO Cecilia Schéele has been appointed CFO and deputy CEO of the Company.

Company description
Following completion of the Transaction, the Company’s business consists of the business currently conducted by Flerie. In light of the substantial change in operations that the Transaction entails, the Company published a company description on May, 27 2024 with information about, inter alia, Flerie, InDex Pharmaceuticals, and the Transaction. The company description is available on Flerie’s website: www.flerie.com.

Admission to trading on Nasdaq Stockholm
In connection with completion of the Transaction, the Company intends to carry out an uplisting from Nasdaq First North Growth Market to Nasdaq Stockholm. The Company will prepare and publish a prospectus for admission to trading of the Company’s share on Nasdaq Stockholm. The prospectus is intended to be registered by the Swedish Financial Supervisory Authority and published around June 26, 2024. The first day of trading on Nasdaq Stockholm is planned to take place around June 27, 2024.