On June 20, 2023 Geron Corporation (Nasdaq: GERN), a late-stage clinical biopharmaceutical company, reported the submission to the United States Food and Drug Administration (FDA) of a New Drug Application (NDA) for imetelstat for the treatment of transfusion-dependent anemia in adult patients with low- to intermediate-1 risk myelodysplastic syndromes (MDS) who have failed to respond or have lost response to or are ineligible for erythropoiesis-stimulating agents (ESAs) (Press release, Geron, JUN 20, 2023, View Source [SID1234632794]).

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"This pioneering achievement to submit the first New Drug Application to the FDA for a telomerase inhibitor reflects the dedication, commitment and teamwork of so many people who believed targeting telomerase could make a significant difference for patients," said John A. Scarlett, M.D., Chairman and Chief Executive Officer. "We are deeply committed to addressing the unmet needs for lower risk MDS patients, who often suffer from transfusion-dependent anemia."

The NDA submission is based on results from IMerge Phase 3, in which the primary endpoint of 8-week transfusion independence (TI) was significantly higher with imetelstat vs. placebo (P<0.001), with median TI duration approaching one year for imetelstat 8-week TI responders. Mean hemoglobin levels in imetelstat-treated patients increased significantly (P<0.001) over time compared to placebo patients. Further, statistically significant and clinically meaningful efficacy results were achieved across key MDS subgroups: ring sideroblast (RS) status, baseline transfusion burden and IPSS risk category. Safety results were consistent with prior imetelstat clinical experience.

As allowed under imetelstat’s Fast Track designation in lower risk MDS, Geron has requested that the FDA grant Priority Review of the NDA. Under standard practice, Geron expects FDA communication in 60 days whether the NDA was accepted for review and the timeline of such review (i.e., priority or standard). Additionally, based on IMerge Phase 3, Geron expects to submit a Marketing Authorization Application (MAA) in the EU in the second half of 2023.

About IMerge Phase 3

The Phase 3 portion of the IMerge Phase 2/3 study is a double-blind, 2:1 randomized, placebo-controlled clinical trial to evaluate imetelstat in patients with IPSS Low or Intermediate-1 risk (lower risk) transfusion-dependent MDS who were relapsed after, refractory to, or ineligible for, erythropoiesis stimulating agent (ESA) treatment, had not received prior treatment with either a HMA or lenalidomide and were non-del(5q). To be eligible for IMerge Phase 3, patients were required to be transfusion-dependent, defined as requiring at least four units of packed red blood cells (RBCs), over an eight-week period during the 16 weeks prior to entry into the trial. The primary efficacy endpoint of IMerge Phase 3 is the rate of red blood cell transfusion independence (RBC-TI) lasting at least eight weeks, defined as the proportion of patients without any RBC transfusion for at least eight consecutive weeks since entry to the trial (8-week TI). Key secondary endpoints include the rate of RBC-TI lasting at least 24 weeks (24-week TI), the duration of TI and the rate of hematologic improvement erythroid (HI-E), which is defined under 2006 IWG criteria as a rise in hemoglobin of at least 1.5 g/dL above the pretreatment level for at least eight weeks or a reduction of at least four units of RBC transfusions over eight weeks compared with the prior RBC transfusion burden. A total of 178 patients were enrolled in IMerge Phase 3 across North America, Europe, Middle East and Asia.

About Imetelstat

Imetelstat is a novel, first-in-class telomerase inhibitor exclusively owned by Geron and being developed in hematologic malignancies. Data from non-clinical studies and clinical trials of imetelstat provide strong evidence that imetelstat targets telomerase to inhibit the uncontrolled proliferation of malignant stem and progenitor cells in myeloid hematologic malignancies resulting in malignant cell apoptosis and potential disease-modifying activity. Imetelstat has been granted Fast Track designation by the U.S. Food and Drug Administration for both the treatment of adult patients with transfusion dependent anemia due to Low or Intermediate-1 risk MDS that is not associated with del(5q) who are refractory or resistant to an erythropoiesis stimulating agent, and for adult patients with Intermediate-2 or High-risk MF whose disease has relapsed after or is refractory to janus associated kinase (JAK) inhibitor treatment. Geron submitted a New Drug Application (NDA) in the U.S. in June 2023 and expects to submit a Marketing Authorization Application (MAA) in the EU in the second half of 2023 in the lower risk MDS indication. Imetelstat is currently not approved by any regulatory authority.

On June 20, 2023 Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, reported positive top-line results from the pivotal BLUE-C study (Press release, Exact Sciences, JUN 20, 2023, View Source [SID1234632793]). The results show that next-generation Cologuard met all study endpoints and improved every top-line metric, including a 30 percent lower false positive rate, when compared to DeeP-C, the FDA registrational trial for Cologuard.

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Madison Haag, clinical laboratory specialist, loads samples for one step of the Cologuard testing process at one of Exact Sciences’ Madison labs.

"Cologuard is a groundbreaking innovation in non-invasive cancer detection. Next-generation Cologuard will set a new performance standard," said Kevin Conroy, chairman and CEO of Exact Sciences. "We are harnessing deep scientific insights, advanced technology, and over a decade of research and development to detect colorectal cancer with greater sensitivity and significantly improve the false positive rate. Once approved, next-generation Cologuard will meaningfully enhance the patient experience, and it comes at a critical time – when there are 60 million Americans not up to date with screening."

About the BLUE-C Study
BLUE-C is a multi-center, prospective study (NCT04144738) of more than 20,000 adults 40 years of age and older. The trial was designed to evaluate the performance of next-generation Cologuard (multi-target stool DNA or mt-sDNA). Using colonoscopy as a reference method, the robust study design directly compares multiple screening tests, including next-generation Cologuard and a fecal immunochemical test (FIT). Blood samples were also collected for later evaluation of a blood-based screening test being developed by Exact Sciences. BLUE-C is one of the largest colorectal cancer screening trials ever conducted, and the study population reflects the racial and ethnic makeup of the United States according to the 2020 census.

"Accurate and early detection of colorectal cancer and precancerous lesions is critical for reducing incidence and preventing deaths from this disease," said Thomas F. Imperiale, MD, Professor of Medicine at the Indiana University School of Medicine, research scientist at the Regenstrief Institute, and principal investigator for BLUE-C. "The results from this large study of a representative population provide affirmation that Exact Sciences continues at the forefront of non-invasive screening. These new results suggest improved performance of an mt-sDNA test, strengthening the case for molecular stool-based testing."

About Next-generation Cologuard
Developed in partnership with Mayo Clinic, next-generation Cologuard features novel biomarkers and improved laboratory processes. It also incorporates enhanced sample stability components to provide patients more time to return their sample to Exact Sciences’ lab and increase the valid result rate.

Cologuard revolutionized colorectal cancer screening by providing a convenient and accurate testing option for those at average risk. Nearly a decade later, Cologuard has been used to screen for colorectal cancer more than 12 million times.

In the coming months, Exact Sciences plans to release additional analyses of the BLUE-C data and complete its application to the FDA for approval of next-generation Cologuard.

About Cologuard
Results from Exact Sciences’ prospective, 90-site, point-in-time, 10,000-patient pivotal trial, DeeP-C, were published in the New England Journal of Medicine in March 2014. The Cologuard test is included in the American Cancer Society’s (2018) colorectal cancer screening guidelines and the recommendations of the U.S. Preventive Services Task Force (2021) and National Comprehensive Cancer Network (2023). The Cologuard test is indicated to screen adults 45 years of age and older who are at average risk for colorectal cancer by detecting certain DNA markers and blood in the stool. Do not use the Cologuard test if you have had precancer, have inflammatory bowel disease and certain hereditary syndromes, or have a personal or family history of colorectal cancer. The Cologuard test is not a replacement for colonoscopy in high-risk patients. The Cologuard test performance in adults ages 45-49 is estimated based on a large clinical study of patients 50 and older. The Cologuard test performance in repeat testing has not been evaluated.

The Cologuard test result should be interpreted with caution. A positive test result does not confirm the presence of cancer. Patients with a positive test result should be referred for colonoscopy. A negative test result does not confirm the absence of cancer. Patients with a negative test result should discuss with their doctor when they need to be tested again. Medicare and most major insurers cover the Cologuard test. For more information about the Cologuard test, visit cologuardtest.com. Rx only.

On June 20, 2023 Eli Lilly and Company (NYSE: LLY) and DICE Therapeutics, Inc. (NASDAQ: DICE) reported a definitive agreement for Lilly to acquire DICE (Press release, Eli Lilly, JUN 20, 2023, View Source [SID1234632792]).

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DICE is a biopharmaceutical company that leverages its proprietary DELSCAPE technology platform to develop novel oral therapeutic candidates, including oral IL-17 inhibitors currently in clinical development, to treat chronic diseases in immunology.

"In combination with its novel technology and expertise in drug discovery, DICE’s talented workforce and passion for innovation will enhance our efforts to make life better for people living with devastating autoimmune diseases," said Patrik Jonsson, executive vice president, president of Lilly Immunology and Lilly USA, chief customer officer. "We welcome DICE colleagues to Lilly and, together, we can tackle the challenges ahead in finding new treatments for patients with significant unmet medical needs."

Kevin Judice, Ph.D., CEO of DICE Therapeutics, added: "We’re eager to see our pipeline, including our oral IL-17 inhibitors, DC-806 and DC-853, benefit from Lilly’s resources and global reach and I’m excited by the prospect of watching these two talented teams in a united quest for scientific innovation. Our novel approach to discovering and advancing oral, small molecules against validated protein-protein interaction targets has even greater potential with Lilly’s industry-leading clinical development capabilities to get these medicines to patients suffering from autoimmune diseases."

Terms of the Agreement
Lilly will commence a tender offer to acquire all outstanding shares of DICE for a purchase price of $48 per share in cash (an aggregate of approximately $2.4 billion) payable at closing. The transaction has been approved by the boards of directors of both companies.

The transaction is not subject to any financing condition and is expected to close in the third quarter of 2023, subject to customary closing conditions, including receipt of required antitrust clearance and the tender of a majority of the outstanding shares of DICE’s common stock. Following the successful closing of the tender offer, Lilly will acquire any shares of DICE that are not tendered in the tender offer through a second-step merger at the same consideration as paid in the tender offer.

The purchase price payable at closing represents a premium of approximately 40% to the 30-day volume-weighted average trading price of DICE’s common stock ended on June 16, 2023, the last trading day before the announcement of the transaction. DICE’s Board of Directors unanimously recommends that DICE’s stockholders tender their shares in the tender offer.

Lilly will determine the accounting treatment of this transaction as a business combination or an asset acquisition, including any related acquired in-process research and development charges, according to Generally Accepted Accounting Principles (GAAP) upon closing. This transaction will thereafter be reflected in Lilly’s financial results and financial guidance.

For Lilly, Kirkland & Ellis LLP is acting as legal counsel. For DICE, Centerview Partners LLC is acting as exclusive financial advisor and Fenwick & West LLP as legal counsel.

On June 20, 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 it has commenced its 64Cu/67Cu SAR-Bombesin Phase I/II trial in metastatic castrate resistant prostate cancer (mCRPC) with the opening of the first site at BAMF Health, Inc in Michigan (Press release, Clarity Pharmaceuticals, JUN 20, 2023, https://www.claritypharmaceuticals.com/news/combat_commences-us/ [SID1234632791]).

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COMBAT (Copper-67 SAR Bombesin in metastatic castrate resistant prostate cancer, NCT05633160)1 is a dose escalation and cohort expansion trial for up to 38 participants. The aim for the trial is to determine the safety and efficacy of 67Cu-SAR-Bombesin in participants with gastrin-releasing peptide receptor (GRPr) expressing mCRPC in patients who are ineligible for therapy with 177Lu PSMA-617.

Clarity’s Executive Chairman, Dr Alan Taylor, commented, "We are excited to initiate our first theranostic clinical trial of the SAR-Bombesin product. COMBAT is our third theranostic trial in the US and a second theranostic trial in prostate cancer, an indication that continues to have a high unmet need. In the VISION trial for the recently approved 177Lu PSMA-617, median overall survival increased from approximately 11 months on standard of care therapy to approximately 15 months with 177Lu PSMA-617 plus standard of care. Despite this, around a quarter of men with mCRPC do not have PSMA-expressing lesions, making it impossible to offer PSMA-targeted products as therapy for this group of patients. As a very large proportion of prostate cancers express GRPr, SAR-Bombesin is an exciting new prospect for better treating these patients that have few therapeutic options at present in the face of a devastating diagnosis.

"We look forward to progressing the COMBAT trial and building on the compelling data from our preclinical studies as well as from three diagnostic trials with this product. SAR-Bombesin has already resulted in improvements to the management of prostate cancer for patients with PSMA-negative or low PSMA expressing tumours and we hope to confirm its safety and efficacy in the theranostic 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.

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 25% of mCRPC patients have low or no uptake of a PSMA-targeting tracer.9 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. The SAR-Bombesin product could offer valuable imaging and therapeutic options for not only PSMA-negative patients, but also the large number of patients that have the target receptor on their cancers.

On June 19, 2023, Kelun-Biotech reported that the innovative TROP2-ADC (SKB264, also known as MK-2870), which is being developed in collaboration with MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA), in combination with pembrolizumab (KEYTRUDA, MSD’s anti-PD-1 therapy) for Phase II clinical studies in select patients with a variety of advanced solid tumors, has been approved for clinical trials in the European Union (Press release, Kelun, JUN 19, 2023, View Source(mk-2870)-is-approved-for-clinical-trials-in-the-european-union [SID1234633517]). This is an international multicenter clinical study which is currently approved in multiple countries and territories, including China, the United States, Canada, Australia, and now the European Union, fully demonstrating the strength of Kelun-Biotech in conducting clinical studies on a global scale. MSD and Kelun-Biotech are working closely to continually advance the international development of SKB264.

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At present, immune checkpoint inhibitors, mainly represented by anti-PD-1/PD-L1 therapies, have played an important role in treating cancer across a variety of tumors. In order to improve outcomes for patients, combination therapies are being explored, including combination with chemotherapy, targeted therapy, radiotherapy, other types of immunotherapy, and more.

ADCs specifically target tumor cells to deliver cytotoxic molecules that induce immunogenic cell death (ICD) and trigger innate and adaptive immune responses, allowing large numbers of T cells to infiltrate tumor cells and thereby improving immunotherapeutic efficacy. Clinical trial data in multiple cancer types have shown that anti-PD-1 therapies in combination with ADCs may be able to improve efficacy compared to either agent alone. TROP2 is highly expressed in a variety of epithelial-derived tumors and can promote tumor cell proliferation, invasion, and metastasis, and is a promising target for broad-spectrum anti-tumor therapy. TROP2-ADCs specifically target TROP2-expressing tumor cells to deliver cytotoxic effects, and have shown encouraging anti-tumor activity as monotherapy in several clinical trials, and has the potential to improve anti-tumor efficacy in combination with immune checkpoint inhibitors such as anti-PD-1/PD-L1 therapies.

About SKB264 (MK-2870)

SKB264 is an innovative ADC targeting TROP2 which was developed by OptiDC, a well-known international ADC R&D platform of Kelun-Biotech, using a proprietary payload-linker strategy (Kthiol design strategy) that achieves an optimized balance of ADC safety and efficacy by combining novel irreversible antibody conjugation chemistry, pH-sensitive payload release mechanisms, and site-specific moderately potent toxin molecules with DAR of 7.4 (novel topoisomerase I inhibitors) [2].

SKB264 (MK-2870) has received 2 Breakthrough Therapy Designations (BTDs) from the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) for the treatment of locally advanced or metastatic triple-negative breast cancer and locally advanced or metastatic EGFR-mutated non-small cell lung cancer who have failed EGFR-TKI therapy.

SKB264 (also known as MK-2870) is currently conducting Phase II and Phase III clinical trials of monotherapy/combination in multiple solid tumors. In China, the Phase III registrational clinical study of SKB264 monotherapy for patients with advanced or metastatic triple-negative breast cancer (TNBC) who have failed at least second-line therapy is progressing smoothly, and it is expected to become the first domestic TROP2-ADC approved for the Chinese market. Phase III clinical studies of SKB264 monotherapy in patients with TKI-resistant and EGFR-mutated non-small cell lung cancer (NSCLC) are also rapidly advancing. Several Phase II clinical studies of SKB264 in combination with pembrolizumab (KEYTRUDA, MSD’s anti-PD-1 therapy) or KL-A167 (Kelun’s anti-PD-L1 monoclonal antibody) are ongoing. Kelun-Biotech has licensed the exclusive rights to MSD (the tradename of Merck & Co., Inc, Rahway, NJ, USA) to research, develop, produce and commercialize SKB264 in all territories outside of Greater China (includes Mainland China, Hong Kong, Macao, and Taiwan).