On October 8, 2024 Medigene AG (Medigene, FWB: MDG1, Prime Standard, ISIN DE000A40ESG2), an oncology platform company specializing in the research and development of T cell receptor (TCR)-directed immunotherapies for the treatment of cancer, reported that it has entered into a Standby Equity Purchase Agreement (SEPA) with a fund managed by Yorkville Advisors Global, LP ("Yorkville") (Press release, MediGene, OCT 8, 2024, View Source [SID1234647088]).

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The SEPA entitles the Company to issue new Medigene shares from authorized capital, excluding shareholders’ subscription rights, and to sell them to Yorkville in several tranches for a total amount of up to EUR 15 million. Medigene may exercise this right at its own discretion and Yorkville is obliged to subscribe for and acquire the requested number of shares in accordance with the terms of the SEPA. The number of shares that can be issued in a single tranche may not exceed the lower of (a) 400,000 shares and (b) 100% of the average daily trading volume during the five trading days immediately preceding the Company’s exercise request.

The subscription price to be paid by Yorkville for each share issued under the SEPA will be equal to 95% of the average of the respective volume-weighted average price of the Medigene share on each of the five trading days following Medigene’s exercise request.

This agreement has a term of 36 months from the date of signing. Yorkville has also entered into a share lending agreement with DJSMontana Holding GmbH, the holding company of Prof. Dr. Dolores Schendel, the Company’s Chief Scientific Officer, pursuant to which DJSMontana Holding GmbH will lend Yorkville 400,000 Medigene shares to support the transaction.

On October 8, 2024 Phanes Therapeutics, Inc. (Phanes), a clinical stage biotech company focused on innovative drug discovery and development in oncology, reported that the first patient has been dosed in the clinical study of PT886 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab) (Press release, Phanes Therapeutics, OCT 8, 2024, View Source [SID1234647089]). The dosing was conducted in a cohort of gastric and gastroesophageal junction cancers.

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As previously announced, Phanes is conducting this study under a clinical trial collaboration agreement with Merck (known as MSD outside the US and Canada). PT886 is a first-in-class native IgG-like bispecific antibody (bsAb) targeting claudin 18.2 and CD47. It was granted orphan drug designation (ODD) for the treatment of pancreatic cancer by the FDA in 2022 and Fast Track designation for the treatment of patients with metastatic claudin 18.2-positive pancreatic adenocarcinoma earlier this year. PT886 is currently being evaluated as monotherapy and in combination with pembrolizumab, or with chemotherapy, either alone or in combination with pembrolizumab.

The multi-center Phase I/II clinical trial of PT886 (NCT05482893), known as the TWINPEAK study, is currently evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy of PT886 in patients with locally advanced or metastatic gastric, gastroesophageal junction and pancreatic cancers. A Phase I clinical trial of PT886 is also ongoing in China (CTR20241655).

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

On October 8, 2024 Pierre Fabre Laboratories, a global player in oncology, and Scorpion Therapeutics, Inc. ("Scorpion"), a pioneering clinical-stage oncology company dedicated to transforming the lives of cancer patients by redefining the frontier of precision medicine, reported that the first patient has been dosed in a Phase I/II, first-in-human dose-escalation, dose-optimization and dose-expansion trial (Press release, Pierre Fabre, OCT 8, 2024, View Source [SID1234647090]). This clinical trial evaluates PFL-241/STX-241, a highly differentiated, orally bioavailable, highly selective tyrosine kinase inhibitor ("TKI") targeting epidermal growth factor receptor ("EGFR") Exon 19 or 21 mutations with the co-occurring C797S mutation, a known resistance mechanism to 3rd generation EGFR inhibitors.

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The PFL-241/STX-241 Phase I/II trial is an open label, multi-center study that aims to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary clinical efficacy of PFL-241/STX-241 as a monotherapy in patients with locally advanced or metastatic non-small cell lung cancer ("NSCLC") harboring EGFR Exon 19 or 21 mutations with the co-occurring C797S mutation.

NSCLC is the most common form of lung cancer and EGFR mutations are one of its most common disease drivers, occurring in up to 38 percent of tumors, depending on geography1,2,3.

"We are eager to begin the clinical evaluation of PFL-241/STX-241, our mutant-selective 4th generation EGFR inhibitor, a molecule with differentiated properties that we believe has the potential to become a best-in-class therapeutic option for patients developing resistance to current targeted therapy," said Francesco Hofmann, Head of Research and Development for Medical Care at Pierre Fabre Laboratories. "The initiation of this clinical trial highlights our team’s engagement and execution in strong partnership with Scorpion Therapeutics, and we look forward to demonstrating how patients could potentially benefit from this targeted therapy."

On October 8, 2024 Rgenta Therapeutics, a biotechnology company pioneering the development of a new class of oral small molecules targeting RNA and RNA regulation for oncology and neurological disorders, reported that the first patients have been dosed in the Phase 1a/b clinical trial of RGT-61159 (Press release, Rgenta Therapeutics, OCT 8, 2024, View Source [SID1234647091]). This novel drug candidate is being developed for the potential treatment of adenoid cystic carcinoma (ACC), colorectal cancer (CRC) and other solid tumors as well as acute myeloid leukemia (AML).

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"Currently, there are no effective systemic treatment options for ACC. Patients with this rare and aggressive cancer, which carries a high risk of recurrence and metastasis, face an urgent need for innovative treatment approaches," said Lillian Siu, M.D., director of the Phase I Program and co-director of the Bras and Family Drug Development Program at the Princess Margaret Cancer Centre, Toronto, Canada. Enrique Sanz-Garcia, M.D., staff medical oncologist and the principal investigator on the trial at the Princess Margaret Cancer Centre added, "The MYB inhibitor, RGT-61159, represents one such innovative approach designed to address the root cause of ACC and we are excited to evaluate this novel drug candidate in this first-in-human Phase 1 clinical trial."

"Patients with colorectal cancer whose disease has failed initial therapy also have poor outcomes," observed Alexander Spira, M.D., Ph.D., chief executive officer and clinical director of NEXT Oncology-Virginia. "RGT-61159 has a novel mechanism of action and targets a known oncogenic driver. We are pleased to collaborate with Rgenta in exploring the potential of this new agent."

"We are excited to move our first asset into the clinic which is a significant milestone for Rgenta, and to work with a group of world-class clinicians on this trial," said Simon Xi, Ph.D., co-founder and chief executive officer of Rgenta. "At Rgenta we have established a platform to discover and develop small molecule RNA targeting medicines with the goal of unlocking the therapeutic potential of historically undruggable targets in human diseases and we look forward to establishing a robust pipeline of clinical assets."

Rgenta’s Phase 1a/b clinical trial of RGT-61159 is a multi-center, open-label study dose escalation and expansion study in patients with advanced relapsed or refractory ACC or CRC. The Phase 1a/b study will evaluate safety, tolerability, pharmacokinetics and target engagement and clinical efficacy of RGT-61159 in patients with ACC or CRC. Additional information about the Phase 1a/b clinical trial can be accessed at ClinicalTrials.gov (NCT06462183).

About RGT-61159
RGT-61159 is an orally available small molecule designed to specifically modulate splicing of the transcription factor MYB resulting in the inhibition of oncogenic MYB protein production, which has the potential to inhibit proliferation or induce cell death of cancer cells that overexpress MYB protein. MYB acts as a master regulator of cell proliferation differentiation processes and its aberrant expression has been demonstrated in multiple forms of human cancer including adenoid cystic carcinoma (ACC), acute myeloid leukemias (AML), T-cell acute lymphoblastic leukemias (T-ALL), colorectal cancer (CRC), small cell lung cancer (SCLC) and breast cancer.

About Adenoid Cystic Carcinoma (ACC)
It is estimated that approximately 200,000 people are living with ACC throughout the world including 11,000 in the US. While it is a rare cancer, ACC is the second most common cancer type arising in the salivary gland and is an aggressive malignancy with a tendency to infiltrate surrounding nerves and metastasize to distant sites. Overactivation of the MYB oncogene has been described as a hallmark of ACC and is noted in over 90% of ACC. Treatment for ACC is extremely challenging and may include surgery and/or radiation, which often fails to control local tumor recurrence and distant metastases. There are no effective targeted therapies available for patients with recurrent and/or metastatic disease. There is thus an unmet medical need for new therapeutic targets and treatment strategies for patients with this fatal cancer.

About Colorectal Cancer (CRC)
CRC is the third most prevalent cancer and the second leading cause of cancer-related mortality worldwide. According to the World Health Organization, in 2022, more than 1.9 million cases of CRC were diagnosed. Despite the improved early detection of CRC and the recent success of targeted therapeutics, approximately 15%-30% of patients present with metastases and 20%-50% of patients with initially localized disease will develop metastases. Patients with relapsed or refractory CRC who have exhausted all the available standard of care therapy options, have a very poor prognosis. MYB is significantly overexpressed in 80-85% of CRC and has been frequently found to be a predictive biomarker of tumor aggressiveness and poor prognosis. Developing novel therapies to treat patients with metastatic CRC remains a major unmet medical need.

On October 8, 2024 Verismo Therapeutics, a clinical-stage CAR-T company developing novel KIR-CAR platform technology, reported that it has activated its CELESTIAL-301 Phase 1 clinical trial at Sarah Cannon Research Institute (SCRI) at Colorado Blood Cancer Institute (CBCI) (Press release, Verismo Therapeutics, OCT 8, 2024, https://www.prnewswire.com/news-releases/verismo-therapeutics-announces-the-activation-of-its-celestial-301-clinical-trial-at-colorado-blood-cancer-institute-302269554.html [SID1234647092]). CBCI offers clinical trials through SCRI, one of the world’s leading oncology research organizations conducting community-based clinical trials. CBCI is the largest and most experienced full-service blood and marrow transplant program in Colorado and among the top programs in the country, making it an ideal location for this clinical trial.

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CELESTIAL-301 will assess safety, tolerability, and preliminary efficacy of SynKIR-310 in patients with relapsed/refractory (r/r) B-cell Non-Hodgkin Lymphomas (B-cell NHL), including Diffuse Large B Cell lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), and Marginal Zone Lymphoma (MZL). The Phase 1 multicenter clinical trial will enroll patients who previously received CAR T therapy but who have since relapsed or become refractory to it as well as patients who never received CAR T therapy.

CELESTIAL-301 trial seeks to address several areas of high unmet medical need. Commercially approved CAR T cell therapies have shown impressive high initial response rates in blood cancers. Over time, however, these therapies result in relapse in an estimated 40-50% of patients1. Such relapses are in part due to lack of long-term T cell effector function and persistence. There are currently very limited treatment options for patients with r/r DLBCL who relapse following treatment with commercial CAR T cell therapies. Ongoing clinical investigations into new and/or salvage therapies for these patients have not yet addressed the unmet medical need.

SynKIR-310 relies on Verismo’s unique KIR-CAR platform and proprietary CD19 binder (DS191). SynKIR-310 is directed by DS191 to target a similar epitope of CD19 as the commercially approved CAR T therapies, with the added potential to prolong the anti-tumor T cell function and persistence. This could potentially improve KIR-CAR T Cell persistence and prevent early disease relapse in patients with aggressive lymphomas.

"This trial embodies Verismo’s continued commitment to combatting advanced cancers and addressing high areas of unmet medical need," said Dr. Laura Johnson, CSO of Verismo Therapeutics. "SynKIR-310 has significant potential to help patients with B-cell Non-Hodgkin Lymphomas and be especially beneficial for patients that relapsed after previous infusions of CAR T cell therapies."

Verismo achieved IND clearance from the FDA in May 2024 to proceed with this multicenter clinical trial investigating SynKIR-310. SynKIR-310 is Verismo’s second clinical pipeline following SynKIR-110, which targets aggressive mesothelin-expressing solid tumors. For more information about the CELESTIAL-101 clinical trial, please visit ClinicalTrials.gov: NCT06544265.

About the KIR-CAR Platform
The KIR-CAR platform is a multi-chain CAR T cell therapy and has been shown in preclinical animal models to be capable of maintaining antitumor T cell activity even in challenging tumor microenvironments. Using NK cell derived KIR and DAP12 split signaling provides a novel combined activation and co-stimulation separate from the usual T cell stimulation pathways. It also enables sustained chimeric receptor expression and improves KIR-CAR T cell long term function. This results in prolonged T cell functional persistence and leads to regression of solid tumors and blood cancers in preclinical models that are resistant to traditional CAR T cell therapies. The KIR-CAR platform is being investigated in combination with many additional emerging technologies to potentially provide the next-generation multimodal targeted immunotherapy for patients in need.